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EMBRYOLOGY
BASICS OF EMBRYOLOGY
FOR VETERINARY MEDICINE STUDENTS
MVDr. Irena Kociánová, PhD.
prof. MVDr. František Tichý, CSc.
University of veterinary and pharmaceutical sciences
Department of anatomy, histology and embryology
Brno 2014
UNIVERSITY OF VETERINARY
AND PHARMACEUTICAL SCIENCES BRNO
FACULTY OF VETERINARY MEDICINE
Department of anatomy, histology and embryology
EMBRYOLOGY
BASICS OF EMBRYOLOGY FOR VETERINARY
MEDICINE STUDENTS
MVDr. Irena Kociánová, PhD.
prof. MVDr. František Tichý, CSc.
BRNO 2014
PREFACE
This textbook provides veterinary students fundamental information to an understanding of
the sequential stages of an embryonic and foetal development. Gametogenesis, fertilisation,
cleavage and gastrulation are presented in sequential chapters. Subsequent chapters deal with
formation of foetal membranes, placentation and establishment of body plan. Body systems,
organogenesis, are considered in separate chapters.
Throughout the textbook the emphases is placed on the origin and differentiation of tissues
and organs and their relationship to each other. The interspecies differences are taken in
account. Fundamental is description of domestic animals development, but especially in
organogenesis the data about birds are mentioned. Drawings and diagrams are used to provide
a clear understanding of information contained in the text.
A study of embryology offers the students an understanding of the normal development and
relationships of tissues and organs and also an understanding of developmental defects and
the clinical conditions to which they give rise. The knowledge of embryology presents the
base for study of topographical anatomy and pathological anatomy.
For encompassment of this discipline is necessary to complete text with the knowledge
obtained at the lectures.
For the compilation of this text were also used information published in some foreign
textbooks (see References and Further Reading)
ACKNOWLEDGEMENTS
We would like to thank Doc. Sedláčková for careful reading and control of the text. Special
thanks go to Doc. Luděk Vajner for repeated checking and assistance with repairs of the text
and helpful comments.
Brno, September 2014
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1 INTRODUCTION
Embryology (from Greek embryon, “the unborn embryo“, and logia) is the science of the
development of an embryos; however, the term generally refers to prenatal development of
embryos and foetuses. In time frame, it can cover the study of an organism´s lifespan.
Ontogeny (also ontogenesis or morphogenesis) describes the origin and development of an
organism from the fertilization of the ovum to the mature form, while phylogeny refers to the
evolutionary history of species and evolutionary relationships among groups of organisms
(e.g. species, populations).
Currently, embryology has become an important research area for studying the genetic control
of the development process (e.g. morphogens), its link to cell signalling and its importance for
the study of certain diseases and mutations and in links to stem cell research.
Embryogenesis is the process by which the embryo is formed and develops, until it develops
into a foetus. Embryogenesis always starts with the fertilization of the ovum (or egg) by
sperm. The fertilized ovum is referred to as a zygote. The zygote undergoes rapid mitotic
divisions with no significant growth (a process known as cleavage) and cellular
differentiation, leading to development of an embryo.
By present-day conception, the development of individual, ontogenesis starts by progenesis.
Progenesis describes origin, development and maturation of gametes (gametogenesis) within
an organism before it has reached physical and sexual maturity. This phase includes
fertilization and finishes by formation of the zygote.
The next period of ontogenesis is blastogenesis, the development of an embryo during
cleavage and germ layers formation. During blastogenesis the basic body plan and domains of
gene expression are established and the developmental fate of all parts of the embryo is
determined. This process proceeds at the proximal portion of the oviduct, later in the uterus.
Blastogenesis includes following stages:
Origination of a morula – the zygote divides to two blastomeres, which divide
repeatedly, producing spherical mass of cells, named the morula.
Blastulation – the final stage of cleavage, characteristic by formation of a blastula,
which consists of a single layer of cells lining a central cavity known as the blastcoele.
Gastrulation – creation of first two germinal layers, ectoderm and endoderm
Notogenesis – the formation of the third germinal layer, mesoderm, and notochord
The third stage of ontogenesis is morphogenesis, which includes the development of organs
and their systems, organogenesis, and the development of tissues, histogenesis.
The ontogenic development does not finish in time of birth, but it continues postnatally by the
processes of maturation and puberty (evolution), ageing process (regression and involution)
and is finished by the physiological death.
The adult mammal body is composed of more than 230 different cell types, all originating
from a single cell, the fertilized egg or zygote. The process during which more specialized
cells develop from less specialized cell types is known as cell differentiation. The processes
preceding cell differentiation are cell specification and cell determination. The labile,
reversible phase referred to as cell specification is followed by an irreversible one, called cell
determination. Once cell is determined, its fate is fixed and it will irrevocably differentiate.
The cell differentiation is ultimately regulated through differential gene expression.
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2 GAMETOGENESIS
The process, by which the maternal and paternal gametes are produced from the primordial
germ cells, is referred to as gametogenesis. Primordial germ cells in the endoderm of the yolk
sac migrate via the dorsal mesentery to the developing gonads. During the migration they
undergo mitosis, producing large number of germ cells which populate gonads. The
subsequent process, gametogenesis, includes meiosis, to allow for recombination of genetic
material and for reduction of the number of chromosomes from the diploid to the haploid
complement, and cytodifferentiation, to achieve the cellular structure characteristic of the
female or male gamete.
2.1. Spermatogenesis
Spermatogenesis may be subdivided into two phases: spermiocytogenesis and
spermiohistogenesis (spermiogenesis).
Spermiocytogenesis is the process whereby spermatogonia are transformed into haploid
spermatids.
The spermatids are gradually transformed (cytodifferentiation) into mature sperms
(spermatozoa) by the process known as spermiohistogenesis.
The entire process of spermatogenesis takes approximately 2 months (40 – 60 days). It starts
at the time of puberty (in bull at 7th month, in ram at 6th month, in boar and buck at 5th
month, in stallion at 12th month).
After arriving in the male developing gonad, the primordial germ cells undergo a series of
mitotic divisions producing stem cells which in association with mesodermal primitive
sustentacular cells (progenitors of Sertoli cells) form seminiferous cords. In this location, they
remain quiescent until the onset of puberty. Shortly before puberty the solid cell cords acquire
a lumen and develop into the seminiferous tubules. The dormant germ cells become
activated and, through the series of mitotic divisions, produce clones of cells referred to as the
type A spermatogonia. Subsequently, some type A cells divide, giving rise to type B
spermatogonia, from which primary spermatocytes differentiate. In parallel, the
sustentacular cells gradually achieve the characteristics of Sertoli cells. Sertoli cells lining the
seminiferous tubules support and nourish the germ cells and they may be involved in the
regulation of spermatogenesis. Primary spermatocytes, the largest germ cells in the
seminiferous tubules, undergo a reduction division, i.e. the first meiotic division, to form two
haploid secondary spermatocytes. Subsequently, the secondary spermatocytes undergo the
second meiotic division, to form four haploid spermatids. (Fig. 2.1) Throughout all these
levels of spermiocytogenesis, from the type B spermatogonia to the spermatids, cytokinesis is
incomplete, leaving all cells within a generation still connected by thin cytoplasmic bridges.
Tight junctions between neighbouring Sertoli cells divide seminiferous tubules into basal
compartments and adluminal compartments, thereby preventing the entry of cells involved in
the generation of immunological responses into the adluminal compartments, and penetration
of macromolecules from adluminal compartments into the animal´s circulation. The structures
which isolate the cells in the adluminal compartment from the testicular vascular supply
constitute the blood-testis barrier.
Haploid spermatids or spermatozoa are extruded from the apical portions of Sertoli cells
into the lumen of the seminiferous tubules. This process is referred to as spermiation. Prior to
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their release, most of the cytoplasm of the immature spermatozoa is shed and phagocytised by
Sertoli cells. Only small amount of cytoplasm, the protoplasmic droplet, remains attached
Period of
multiplication
primordial germ cell (2n)
stem cells
(2n)
spermatogonia A
(2n)
spermatogonia
A
spermatogonia B
(2n)
primary
spermatocyte
(2n)
Period of
growth
secondary
spermatocyte
(1n)
Period of
maturation
spermatids
(1n)
spermatozoa (1n)
residual bodies
Figure 2.1 Stages of the development of spermatozoa from a primordial germ cell.
One spermatogonium B gives rise to 4 spermatozoa.
to the middle piece of the immature spermatozoon. The spermatozoa inside the seminiferous
tubules are immotile and are carried passively by the testicular fluid to the rete testis and
farther into the ductules of epididymis, through the ciliary action of epithelial cells and the
contractions of the smooth muscle of the duct wall.
The transformation of spermatids (Fig. 2.2) into spermatozoa (spermiohistogenesis)
comprises:
1) Golgi phase, during which acrosomal granules are synthesised.
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2) Cap phase - formation of single large acrosomal vesicle by fusion of granules.
A
D
Golgi
aparatus
acrosome
head
nucleus
vagina
mitochondria
mitochondrialis
B
middle
piece
centrioles
C
axial
filaments
centrioles
tail
mitochondrial
alignment
fibrous
sheet
axonema
flagellum
Figure 2.2 Spermatohistogenesis - the morphological changes by which a
spermatid is converted into a spermatozoon
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3) Acrosomal phase - when the acrosomal vesicle covers the anterior aspect of condensed
nucleus, it is referred to as acrosome. The acrosome contains hydrolytic enzymes necessary
to the penetration of the investments of the oocyte.
4) Migration of the centriole pair to the opposite pole of the nucleus, where the proximal
centriole becomes attached to the nucleus and the distal centriole gives rise to the complex of
the axial filaments, so called axonema.
5) Mitochondria accumulate in the proximal region of the axonema forming heliciform
structure (mitochondrial vagina) in the middle piece of the spermatozoon. This structure
functions later like the source of energy for the movement of flagella.
6) Maturation phase, during which the species-specific arrangement of the sperm head and tail
is developed. The maturation process is finished during the passage of spermatozoa through
epididymis. It confers on them the ability to fertilise an ovum.
2.2. Oogenesis
After arriving and proliferation in the developing ovary, the primordial germ cells become
surrounded by pre-follicular cells - flat cells derived from the surface epithelium of the
developing ovary. That turns the primordial germ cells into oogonia and pre-follicular cells
into squamous follicular cells. Subsequently, oogonia continue to proliferate leaving
interconnected to each other by cytoplasmic bridges. When oogonia have completed their
cycles of mitosis (period of multiplication) (Fig. 2.3), some of them enter the prophase of
the first meiotic division and become primary oocytes which are diploid (period of growth).
They become arrested at the diplotene phase. A primary oocyte surrounded by a single layer
of squamous follicular cells is known as a primordial follicle. The primordial follicles
present the pool of quiescent follicles from which the female will recruit follicles for growth
and ovulation for the rest of her reproductive life. The number of primordial follicles with
oogonia may be hundreds of thousands but during both the proliferative and resting phase, a
high number of primordial follicles undergo atresia.
During puberty, completion of the first meiotic division follows hormonal stimulation. The
oocyte increases in size and surrounding follicular cells form a stratified layer around the
oocyte. The follicular cells are now referred to as granulosa cells. With this activation the
period of growth begins. The oocyte grows from less than 30 µ to more than 120 µ in
diameter and granulosa cells form several layers around the oocyte. This structure is known as
the secondary follicle. The oocyte and the surrounding granulosa cells synthesize
glycoproteins, which form zona pellucida around the oocyte. Numerous projections of the
innermost granulosa cells penetrate through the zona pellucida and enter in contact with the
oocyte by gap junctions. The stromal cells surrounding the granulosa cells differentiate into
an inner, steroid producing layer, theca interna and the outer theca externa. Subsequently
the antrum folliculi forms by fusion of fluid-filled spaces into a single cavity. Due to
expansion of antrum the oocyte with surrounding granulosa cells remains attached to the
follicular wall. This structure protruding into the antrum folliculi is referred as cumulus
oophorus. Those granulosa cells which surround the oocyte in a radial fashion are referred to
as the corona radiata. Thus the mature, tertiary or Graafian follicle is established.
Rupture of the Graafian follicle and release of the oocyte from the follicle with its coverings
is referred to as ovulation. Ovulation occurs spontaneously in most animal species
(spontaneous ovulation) or may be induced by coitus (induced ovulation). It is in cat, rabbits,
ferrets and camels. The number of released ova is characteristic for individual species and is
strongly influenced by genetic factors.
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The subsequent process of differentiation of the primary oocyte is period of maturation. The
completion of the first meiotic division results in creation of two haploid cells of unequal size.
The cell which receives most of the cytoplasm is referred to as secondary oocyte and the
other, which receives a minimal amount of cytoplasm, is the first polar corpuscle. The
secondary oocyte immediately enters the second meiotic division, which has a character of
mitosis. It results in formation of two haploid cells, the ovum and the second polar
corpuscle. Completion of the second meiotic division occurs after fertilization. In case of
failing fertilization the secondary oocyte becomes extinct.
After ovulation, the ovum enters the uterine tube, the site of fertilization, where by means of
wall contractions and ciliary beat is shifted along the tube towards the uterus.
primordial germ cell (2n)
Period of
multiplication
oogonia
(2n)
Period
of
growth
primary
oocyte (2n)
ovulation
secondary oocyte (n) and
first polar corpuscle (n)
Period of
maturation
ovum (n) and secondary
polar corpuscle (n)
fertilisation
zygote (2n)
fusion of male and
female pronuclei
Figure 2.3 Oogenesis begins in foetal life, at the prophase of first meiotic division is
interrupted, and does not continue until females are sexually matured. During oogenesis
one diploid oogonium gives rise to only one ovum and polocytes die.
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3 SEXUAL MATURITY AND SEXUAL CYCLE
Sexual maturity is the stage at which an organism can reproduce. Male and female
reproductive organs mature and become be able to produce gametes. It may also be
accompanied by a growth spurt or other physical changes which distinguish the immature
organism from its adult form. These are termed secondary sex characteristics and often
represent an increase in sexual dimorphism.
Achieving of this stage, puberty, takes different time in animal species and is influenced by
conditions of external and inner environment - wild animals achieve the puberty earlier than
domestic.
The sexual maturity in animals is manifested by oestrous cycle, which comprises the
recurring physiologic changes that are induced by reproductive hormones. The oestrous
cycles are interrupted by anoestrous phases or pregnancies and continue until death. Some
animals may display bloody vaginal discharge, often mistaken for human menstruation.
According to the frequency of the oestrous cycle the animals differ to:
Monoestrous – animals that have only one oestrous cycle per year (wild animals –
wolves, foxes, bear)
Dioestrous – animals that have the oestrus twice per year (dog, cat)
Polyestrouso – in the most domestic animals the oestrus is recurring periodically,
usually by three weeks and takes 1 – 2 days, in mare 2 - 10 days
(cattle, pigs, mouse, rat)
Seasonally polyoestrous – they have more than one oestrous cycle during specific
time of the year
Short-day breeds (sheep, goats, deer, and elk) are sexually active in autumn or winter.
Long-day breeds (horses and hamsters) are sexually active in spring and summer.
A few mammalian species, such as rabbits, do not have the oestrous cycle and the ovulation is
stimulated by the cohabitation.
The timing of oestrus in wild animals is coordinated with seasonal availability of food, and
other circumstances such as migration, predation etc., the goal being to maximize the
offspring's chances of survival. Some species are able to modify their oestral timing in
response to external conditions.
The oestrous cycle is characterized by the complex of changes on reproductive system
organs (ovary, uterus, and vagina) and is accompanied by the behavioural changes.
3.1. The phases of the oestrous cycle
1) proestrus
- the first phase in the oestrous cycle immediately before oestrus is characterized by
development of both the endometrium and ovarian follicles. The secondary ovarian follicles
start to grow and change to tertiary. The uterine mucous connective tissue and glands
proliferate (under the influence of estrogen), the vascularisation enhances. In the epithelium
of a vagina the synthesis and accumulation of glycogen proceeds. Some animals may
experience vaginal secretions that could be bloody. The female is not yet sexually receptive.
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2) oestrus
- the second phase in the oestrous cycle is characterized by receptivity to a male and to mating
(often referred to as "heat" or "in heat"). Under the regulation by gonadotropic hormones,
ovarian follicles are maturing, ovulation occurred and estrogen secretions exert their biggest
influence. The changes of the uterus mucosa culminate, glands initiate the secretory activity.
In the vagina, superficial epithelial cells are enlarged, the suggestion of a keratinisation occurs
and cell nuclei loose the affinity to dyes.
A signal trait of oestrus is the lordosis reflex, in which the animal spontaneously elevates her
hindquarters.
3) metoestrus
- during this third phase, the signs of estrogen stimulation subside and the corpus luteum
periodicum starts to form at place of the Graaphian follicle rupture. The highly vascularised
uterine mucosa is prepared for seminated egg nidation. In the vagina, superficial epithelial
cells flake off, the epithelium runs low and infiltrates by lymphocytes.
When the semination occurs, becomes pregnancy (gravidity). The corpus luteum periodicum
enlarges and changes to corpus luteum graviditatis ensuring the production of progesterone.
When the semination doesn´t occur, the oestrous cycle continues immediately by dioestrus.
4) dioestrus
- the last phase of the oestrous cycle is characterized, in case of pregnancy, by the functional
corpus luteum graviditatis and the increase in the blood concentration of progesterone. In the
case of the absence of pregnancy the dioestrus phase (also termed pseudo-pregnancy)
terminates with the regression of the corpus luteum. The lining in the uterus is not shed, but
will be reorganised for the next cycle. The vaginal epithelium is low, permeated with the
lymphocytes and neutrophils.
Anoestrus
Not the phase in the oestrous cycle. Sometimes referred to as the phase, when the sexual cycle
rests.
Summary: the most evident changes during the oestrous cycle are observable on the ovary –
the ovarian cycle, the uterus – the uterine cycle and the vagina – the vaginal cycle.
The ovarian cycle is characterized by the maturation of ovarian follicles, their rupture
(ovulation) and by the rise and regression of yellow bodies (corpora lutea). The corpus luteum
develops after the rupture of tertiary (Graafian) follicle from its wall reminder. When the egg
was seminated, so called corpus luteum graviditatis is created. It survives until the end of
pregnancy; however, in the last third of the pregnancy its function is controversial, because
the production of progesterone undertakes a placenta. Progesterone is a steroid hormone
which lowers the contractility of the uterine smooth muscle, protects the next ovulation during
the pregnancy, keeps the uterine mucosa proliferated, decreases the immune response of the
uterus and acts as an anti-inflammatory agent, stimulates the uterine glands secretion and later
milk secretion.
The uterine cycle is a complex of changes, which are in relation with the change of
the uterine mucosa to pars materna placentae. The uterine epithelium increases. The
connective tissue of endometrium initially proliferates under the influence of estrogen and is
hyperaemic with a rich blood supply of spiral arteries. The uterine glands become straighten
and longer and produce the considerable amount of the secretion. In bitch and mare the
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bloody secretion outflow from the genital tract is observable. After the oestrus the changes a
little retreat, except the part of the uterine mucosa, which comes to the contact with the
allantochorionic villi. This part functionally specializes and becomes the part of the placenta.
The vaginal cycle is typical by the cyclic changes of the vaginal epithelium. In
dioestrus the epithelium is thin, mitotic figures are infrequent, leukocytes within the
epithelium are abundant. During the proestrus numerous mitosis are observable, the
epithelium thickens and superficial cells slough off into the lumen. In oestrus superficial
epithelial cells are enlarged, the suggestion of a keratinisation occurs and cell nuclei loose the
affinity to dyes. The cells look like large, irregular, flat and pale plates. In metoestrus deeper
layers of the oestrous epithelium now line the lumen because the older, superficial layers have
been cornified and sloughed off. Reduction of mitotic activity is typical. Leucocytes again
migrate through the epithelium into the lumen.
The vaginal cytology is used to determinate the stage of reproductive cycle. According to
which structures predominate throughout the cycle, its four stages may be grouped into the
follicular phase (proestrus and oestrus) or the luteal phase (dioestrus and anoestrus).
Classification of vaginal epithelial cells:
A majority of cells observed in a normal vaginal smear are, not surprisingly, vaginal
epithelial cells. In addition, varying numbers of leukocytes, erythrocytes and bacteria are
usually evident, and small numbers of other contaminating cells and microorganisms are
sometimes observed.
Analysing a vaginal smear is largely an exercise in classifying the epithelial cells into one of
three fundamental types: parabasal, intermediate or superficial cells. Keep in mind, however,
that the epithelial cells reflect a developmental continuum; some of the cells you observe will
not fit perfectly into these rigidly-defined categories.
Differences from the menstrual cycle
Mammals share the same reproductive system, including the regulatory hypothalamic system
that releases gonadotropin releasing hormone in pulses, the pituitary that secretes follicle
stimulating hormone and luteinizing hormone and the ovary itself releases sex hormones
including estrogens and progesterone. However, species vary significantly in the detailed
functioning. One difference is that animals that have oestrous cycles reabsorb the
endometrium if conception does not occur during that cycle. Animals that have menstrual
cycles shed the endometrium through menstruation instead. Another difference is sexual
activity. In species with oestrous cycles, females are generally only sexually active during the
oestrus phase of their cycle (see above for an explanation of the different phases in an
oestrous cycle). This is also referred to as being "in heat". In contrast, females of species with
menstrual cycles can be sexually active at any time in their cycle, even when they are not
about to ovulate. Humans, unlike other species, were thought to not have any obvious external
signs to signal oestral receptivity at ovulation (concealed ovulation). Recent research
suggests, however, that women tend to have more sexual thoughts and are far more prone to
sexual activity right before ovulation (oestrus).
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4 FERTILIZATION
Fertilization is the process whereby the sperm and the egg (collectively called the gametes)
fuse together to begin the creation of a new individual. Genome of the new individual is a
combination of genes derived from both parents.
In animals two ways of the fertilization are recognised: outer and inner.
1) Outer fertilization – gametes are excluded to the external environment (water), where
fertilization and next development proceed (fish, amphibians)
2) Inner fertilization – the usual site of the fertilization is the ampulla of the uterine tube,
but it may occur in other parts of the tube too, not in uterus. Chemical signals secreted
by the oocyte and surrounding follicular cells guide the capacitated sperms to the
oocyte (chemotaxis)
Although the details of fertilization vary from species to species, generally 4 steps of the
fertilization may be described:
 Contact and recognition between sperm and egg (base on the presence of
gamete-specific proteins)
 Regulation of the sperm entry into the egg
 Fusion of the genetic material of sperm and egg
 Activation of egg metabolism to start development
Defects at any stage in the sequence of events might cause the zygote to die. The fertilization
process takes approximately 24 hours.
The interval during which the mammalian egg may be fertilized ranges from 6 to 16 hours
after the ovulation. As well sperms keep their ability to fertilize the egg for a certain period
after the placing into the female genital ways. This time is longer than in egg, e.g. in bull 30
hours, in horse about 48 hours and in domestic birds up to 3 weeks.
The term fertility mustn´t be confused with the term motility. The sperms, seeming to have
normal movability may not be able to fertilize the egg.
For the fertilization, generally 1 % of ejaculated sperms is sufficient. There are usually more
than 100 million sperms per millilitre of semen (rabbit 200 million, bull 5 milliards) in the
ejaculate of normal males. Sperms account for less than 10 % of the semen. The reminder of
the ejaculate consists of the secretions of the seminal glands, prostate and bulbourethral gland.
4.1. Transport of gametes
Oocyte transport
The secondary oocyte is expelled at ovulation, together with follicular liquid, from the
ruptured Graafian follicle. During the ovulation, the fimbriated end of the uterine tube
becomes closely touch to the ovary. The finger like processes of the tube, fimbriae, „sweep“
the secondary oocyte into the funnel-shaped infundibulum of the uterine tube. The oocyte
passes into the ampulla of the tube, mainly as the result of peristaltic contractions of smooth
muscle cells of the uterine tube wall and the movement of epithelial cells cilia.
Sperm transport
Sperms pass from the uterus into the oviduct by the active movement of their tails.
They move 2 to 3 mm per minute, but the speed varies with the pH of the environment. In
addition, prostaglandins in the semen are thought to stimulate smooth muscle cells in the wall
of the oviduct and uterus and so assist in the movement of sperms to the site of fertilization.
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The course of movement is ensured by the chemoattraction of the sperm to the egg.
Chemical signals (attractants) are soluble molecules secreted by the egg (by the oocyte and
surrounding follicular cells) and they guide the sperms to the oocyte (sperm chemotaxis).
Freshly ejaculated sperms are unable to fertilize the egg. They must firstly undergo the
process of capacitation. During approximately 7 hours the seminal proteins and
glycoproteins are removed from the surface of the sperm´s head and the membrane
components of the sperm and acrosome are extensively altered. The outer acrosomal
membrane changes and comes into the contact with sperm cell membrane in a way that
prepares it for fusion. Capacitated sperms show no morphologic changes, but they are more
active. Completion of capacitation permits the acrosome reaction to occur.
The acrosomal reaction of sperms must be completed before the sperm can fuse with
the oocyte. The initiation of acrosomal reaction is stimulated by the contact of the sperm with
the corona radiata surrounding the egg. The multiple point fusions of the sperm membrane
and the external acrosomal membrane occur and subsequently, the fragmentation of
membranes and formation of vesicles from these membrane fragments is observable. The
changes induced by the acrosomal reaction are associated with the release of enzymes,
including hyaluronidase and acrosin, from the acrosome.
4.2. Phases of fertilization
The process of the fertilization (Fig. 4.1) is a sequence of coordinated events:
1) passage of a sperm through the corona radiata
- dispersal of the follicular cells of the corona radiata appears to result mainly from the
action of the enzyme hyaluronidase released from the acrosome of the sperm. The
movement of the tail of the sperm is also important.
2) penetration through the zona pellucida
- passage of sperm through zona pellucida (an extracellular matrix of glycoproteins) is
also the result of the enzyme action. Enzymes released from the acrosome, acrosin,
esterase and neuraminidase appear to cause lysis of the zona pellucida and formation
of pathway for the sperm (penetration slits).
Once the sperm penetrates the zona pellucida, a cortical reaction occurs. The cortical
reaction changes the properties of the zona pellucida and makes it impermeable to
other sperms.
The prevention of polyspermy
Penetration of more than one spermatozoon into a mammalian ovum, polyspermy, leads to the
death of the zygote. Due to, in mammals, the zona pellucida and vitelline membrane undergo
alteration after entry of the spermatozoon. This change makes these structures impermeable to
additional spermatozoa.
In birds, a number of spermatozoa may enter the avian ovum without endangering zygote
survival. When the pronucleus from one spermatozoon fuses with the female pronucleus, the
other spermatozoa degenerate without any adverse effect on the fertilized ovum.
Cortical reaction - when the sperm penetrates the zona pellucida, some proteins of the
acrosomal membrane bind specifically to the ZP2 glycoprotein of zona pellucida and the
cortical reaction occurs. Cortical granules inside the secondary oocyte (probably lysosomes)
fuse with the plasma membrane of the cell, causing enzymes inside these granules to be
expelled by exocytosis to the zona pellucida. This in turn causes the glycoproteins in the zona
pellucida to cross-link with each other, making the whole matrix hard and impermeable to
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sperm. This prevents fertilization of an egg by more than one spermatozoon. Comparable
changes in the vitelline membrane are referred to as the vitelline block. The hydrolytic
enzymes released by the granules cause the zona reaction, which removes the ZP2 ligands
from the zona pellucida.
The perivitelline space is the space between the zona pellucida and the cell membrane of the
oocyte. In the slow block to polyspermy, the cortical granules released from the ovum are
deposited in the perivitelline space. Polysaccharides released by the granules cause the space
to swell, pushing the zona pellucida farther from the oocyte.
3) fusion of plasma membranes of the oocyte and sperm
- the cell membranes of the oocyte and the sperm fuse and break down at the area of
fusion. In mammals, the sperm contacts the egg not at its tip (as in birds), but on the
side of the sperm head. During the next penetration firstly enter the oocyte the caudal
part of the sperm head and the tail, than lateral and lastly apical portion of the head
(„reverse driving“).
4) completion of second meiotic division of the oocyte and formation of female
pronucleus
- penetration of the oocyte by the sperm activates the oocyte into completing the
second meiotic division and forming a mature oocyte and a second polar body. The
nucleus of the mature oocyte becomes the female pronucleus.
5) formation of male pronucleus
- the nucleus of the sperm enlarges to form the male pronucleus and the tail of the
sperm degenerates. The sperm mitochondria and their DNA are also degraded, so that
all of the new individual´s mitochondria are derived from its mother. Only the sperm
centriole survives and serves for making the new mitotic spindle.
6) fusion of pronuclei and formation of the zygote
- morphologically, the male and female pronuclei are indistinguishable. The oocyte
containing two haploid pronuclei is named ootid. Once the pronuclei fuse to a single
diploid aggregation of chromosomes, the ootid becomes the zygote. The chromosomes
in the zygote arrange to the cleavage spindle.
7) cleavage of the zygote
- spherical, compact nucleoli inside both pronuclei are early observable. Cytoplasmic
organelles accumulate in the vicinity of pronuclei, especially mitochondria, smooth
endoplasmic reticulum and Golgi apparatus. The cell membrane is equipped by the
numerous microvilli protruding into the perivitelline space. The pinocytotic activity is
observable. Subsequently the centrioles separate and move to the opposite poles, the
mitotic spindle is created, the membranes of pronuclei disappear and both sets of
chromosomes form monaster in an equatorial plane. The division adequate to mitosis
becomes with only one the difference that the chromosomes originate from two
pronuclei. This division is actually the first step of embryonic development. The next
cleavage of the zygote consists of repeated mitotic divisions by which the great
number of blastomeres develops.
14
Figure 4.1 Stages of fertilization (1 to 7)
15
4.3. Fertilization disorders (ectopic pregnancy)
The usual side of the fertilization is the ampulla of the uterine tube. An ectopic
pregnancy is a complication of pregnancy in which the embryo implants outside the uterine
cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are
dangerous for the mother, since the internal haemorrhage is a life threatening complication.
The most often ectopic pregnancies occur in the uterine tube - so-called tubal pregnancies.
The embryo adheres to the lining of the Fallopian tube and burrows into the tubal lining. Most
commonly this invades vessels and will cause bleeding. Two percent of ectopic pregnancies
occur in the ovary, the cervix or in the abdomen.
In rare cases of ectopic pregnancy, there may be two fertilized eggs (multipara), one outside
the uterus and the other inside. This is called a heterotopic pregnancy.
4.4. Fertilization in birds
Similarly like in mammals, there is an internal fertilization in birds. Few male birds have a
phallus; the most achieve fertilization via a cloacal kiss. The sperm are ejaculated into the
cloaca or vagina and rely on their motility to reach the numerous sperm-storage tubules
(SSTs) located at the junction of the vagina and the uterus. These sperm storage tubules are
lined with simple columnar epithelium and they can store sperm for long periods of time (10
days to 2 weeks). As a consequence of selection during migration through the vagina, only 1–
2% of sperm enter the SSTs, the rest are probably ejected the next time that the female
defecates. During this storage period the sperm undergo the process of capacitation. The
sperm in the SSTs are invariably positioned with their heads directed towards the distal end of
the tubule. They are lost from the SSTs more or less continuously; they enter the uterus and
move relatively slowly through the oviduct towards its infundibulum. On the ovulation, the
ovum is captured by the funnel-shaped infundibulum and then shifted by the cilia movement
into the next portion of the uterine tube, magnum. The sperm cluster around the surface of
the ovum; their target is the germinal disc, which contains the female pronucleus. At this stage
the ovum is bounded by the inner perivitelline layer. The clustering of sperm around the
germinal disc suggests that sperm might use chemical signals to locate the germinal disc
(chemotaxis).
In contrast to most other taxa, where only a single sperm enters the ovum, polyspermy is
typical in birds. Several sperm enter the germinal disc region, hydrolysing the inner
perivitelline layer via the acrosomal reaction of the sperm, whereby the release of enzymes
from the sperm acrosome enables the sperm nucleus to enter the ovum. However, only a
single spermatozoon fuses with the female pronucleus and the remaining sperm are shifted to
the periphery of the germinal disc and play no further part in development.
The process of the fertilization includes the penetration of the ovum by sperm
(contrary to the mammals the sperm contacts the egg at its tip) as well as the fusion of the
male and female pronuclei (syngamy).
Because embryo development begins almost immediately, many cell divisions have
occurred by the time the ovum has become incorporated into the egg and the egg is laid (in
most species) 24 hr. later.
During the descensus to the uterus the embryo rotates and is enveloped with the albumen (egg
white), membranae papyraceae and the egg shell. The demand for calcium to make the egg
shell is very high, and so the circulating levels of blood calcium in birds are greatly elevated
compared to mammals, typically twice as much.
16
The embryo development is conditioned by the temperature of environment and air
humidity.
4.5. Sex determination
Primary sex determination is the determination of the gonads. In mammals the primary
sex determination is chromosomal.
Humans and other mammals have an XY sex determination system: the Y chromosome
carries a gene responsible for triggering male development (testis-determining factor), that
organizes the gonad primordium into a testis. The default sex, in the absence of the Y
chromosome, is female. The gonadal primordia develop into ovaries. Thus, XX mammals are
female and XY are male.
In birds, which have a ZW sex-determination system, the opposite is true: the W
chromosome carries factors responsible for female development, and default development is
male. In this case ZZ individuals are male and ZW are female.
All somatic cells of the organism and also gametes (spermatogonia, oogonia) at the
beginning of their development are equipped by two sets of chromosomes (autochromosomes)
and two heterochromosomes. In female the heterochromosomes are adequate and are referred
to as XX, in male they are different and are referred to as XY. During meiosis the number of
chromosomes is reduced to half (haploid cells). That is why the matured egg contains in the
nucleus always one X chromosome. By the same way the number of chromosomes is reduced
in spermatozoa, but the sperm may obtain either X or Y heterochromosome. If the egg is
fertilized by the sperm with heterochromosome Y, the male sex originates (XY). After
fertilization by the sperm with heterochromosome X, it results in the female sex (XX).
Because of the number of sperms with X heterochromosome is the same like with Y
heterochromosome, is the sex ratio approximately equal.
Secondary sex determination affects the phenotype outside the gonads. This includes the
male or female duct system and external genitalia. If the Y chromosome is absent, gonadal
primordia develop into ovaries. The ovaries produce estrogen, which enables the
development of the Müllerian duct into the oviduct, uterus and vagina. If the Y chromosome
is present, testes form and secrete two major hormones. The first is anti-Müllerian hormone,
which destroys the Müllerian ducts; the second is testosterone, which stimulates the
formation of male duct system, scrotum and penis.
A freemartin or intersex - freemartinism is the normal outcome of mixed-sex twins in cattle
and it also occurs occasionally in pigs, goat and sheep. Freemartin is an infertile female
individual, which has masculinized behaviour and non-functioning ovaries. Genetically and
externally the animal is female, but it is sterilised during the foetal development by hormones
from a male twin.
17
5 BLASTOGENESIS
Blastogenesis is the period of embryonic development following immediately the fertilization.
It includes periods of cleavage, blastulation, gastrulation and notogenesis.
- cleavage – results in multicellular structure morula
- blastulation – during this period morula changes into saccular formation - blastula
- gastrulation – period of germinal layers origin
- notogenesis - creation of mesoderm and chorda dorsalis
Transition foregoing period to the next is fluent. Period lengths as well as the level of changes
during the development are different in various animal species. Especially the first period of
development, cleavage, characterized by series of mitotic divisions depends on the amount of
yolk inclusions and their position in the egg, that are different in fish, reptiles, birds and
mammals.
Cells rising during cleavage period are named blastomeres. Blastomeres don´t draw apart and
are separated with grooves visible at the surface of morula. They are smaller than mother cell,
immediately dividing again, become smaller and smaller and number of them arises by
geometric progression. By this manner eggs with small amount of yolk divide, e.g. eggs of
placental mammals. The eggs with big amount of yolk, e.g. eggs of birds, divide only
partially, at part where yolk is missing (at so called animal pole).
Otherwise, the mode of cleavage is determined by the amount of yolk and its distribution. On
this basis cleavage may be holoblastic and meroblastic:
 holoblastic - the cleavage in which the segmentation lines pass through the entire egg,
dividing it completely. It occurs in alecithal, microlecithal and
mesolecithal eggs, e.g. frog, human egg etc. It is of two types: equal
holoblastic and unequal holoblastic.
 meroblastic - the lines of segmentation do not completely pass through the egg and
remain confined to a part of the egg. Such type of cleavage is found in
megalecithal eggs as the yolk provides resistance to the cleavage e.g.
insects, reptiles.
Meroblastic cleavage may be discoid and superficial.
According to yolk inclusions content and distribution of them in cytoplasm we can
distinguish:
a) oligolecithal (microlecithal) eggs - with very small amount of yolk (e.g. Amphioxus).
Mammal eggs are secondarily oligolecithal. They lost yolk during phylogenetic
development, because mammal’s embryos obtained easier manner of nutrition from
placenta. Yolk inclusions are equally dispersed in the egg, so the term isolecithal egg
is used. They cleave all over the surface and blastomeres are of the same size. This
manner of cleavage is total equal.
b) mesolecithal eggs – they have little more yolk than previous and are typical for fish
and amphibians. This nutritional storage is used only in early stage of embryonic
development, because germs in larval stage obtain nutrition from outer environment.
In mesolecithal eggs yolk inclusions are distributed unequally; such egg is named
anisolecithal. They still cleave all but blastomeres at the vegetative pole are bigger
(macromeres) than at the animal pole (micromeres). This manner of cleavage is total
unequal.
Oligolecithal and mesolecithal eggs are also named holoblastic eggs, because all the
eggs undergo next embryonic development.
c) Polylecithal (megalecithal) eggs – they are typical by large quantity of the yolk and
occur in some fish and amphibians, in reptiles, oviparous mammals and above all in
18
birds. The yolk inclusions are accumulated at the vegetative pole, whereas at the
animal pole the cytoplasm is devoid of yolk. The inert yolk mass at the vegetal pole
does not divide and the site of cleavage is confined to a disc-shaped area at the animal
pole. Grooves leak into the yolk, where disappear. This manner of cleavage is partial
discoid. Partially grooving eggs are also named meroblastic, because not all the eggs
undergo next embryonic development.
In invertebrates (e.g. articulates and insects) there are centrolecithal eggs. The yolk is
concentrated in the middle portion of egg. These eggs cleave partially, only at the surface
(a layer around centrally positioned yolk) and this manner is named partial superficial
cleavage. (Fig. 5.1)
1
2
3
4
Figure 5.1 Different types of cleavage depending on the yolk inclusions content.
1 - oligolecithal egg grooving totally equally, 2 - mesolecithal egg grooving totally
unequally, 3 - polylecithal egg grooving partially discoidally, 4 - polylecithal egg
grooving partially superficially. Modified from Horký et al. (1984).
19
5.1. Blastogenesis in mammals
5.1.1. Cleavage and blastulation
As noted above, mammal eggs are secondarily oligolecithal and cleave totally equally.
Cleavage consists of repeated mitotic division of the zygote, resulting in a rapid increase in
the number of cells (blastomeres). Division of zygote into blastomeres begins approximately
30 hours after semination. In mare we find bicellular embryo 24 hours after semination, in
cow 40 – 56 hours, in sheep 34 hours, in goat 30 hours and in pig 25 – 46 hours. The first
groove on the seminated egg is meridional and divides zygote to two equivalent halves. Inside
one of them the rest of sperm can be identified. Subsequent cleavage divisions follow one
another, forming progressively smaller blastomeres. The second groove is formed only on the
one blastomere at a right angle to the first, the next on the other. Grooves arise alternately, so
the number of blastomeres is mostly unequal contrary to Amphioxus, where the number of
blastomeres is always even.
After multiple divisions multicellular formation arises (still coated with zona pellucida). Due
to its similarity to mulberry it is named morula. At this early stage in cleavage, the shapes of
blastomeres change as they become compressed against each other. Subsequently, in this „ball
of cells“, we can observe cell phenomenon of compaction. It is probably mediated by cell
surface adhesion glycoproteins. Compaction permits greater cell-to-cell interaction and is a
prerequisite for segregation of the internal cells. Superficial blastomeres are smaller and
lighter and create a coat similar to simple epithelium. Inner blastomeres are rather bigger and
darker and form inner globular mass. Different colour is given by the level of RNA synthesis,
which is higher in inner cells. (Fig. 5.2)
After zona pellucida decomposition superficial cell layer enters in contact with uterus mucosa.
This layer is going to be trophoblast or chorionic ectoderm (trophe = nutrition) and gives
rise to the embryonic part of placenta. Inner cell mass is going to be embryoblast and
presents foundation of embryo and some extraembryonic organs – amnion and yolk sac.
The spherical morula forms approximately 3 days after semination and descends to the uterus.
Shortly after morula enters the uterus (approximately 4 days after semination), fluid-filled
spaces appear inside the morula. The fluid passes from the uterine cavity across the outer cells
of the compact morula to form bigger and bigger spaces, which later fuse to the blastocystic
cavity. Fluid accumulation in the blastocystic cavity is an active process involving sodium
and potassium pump activity. During this stage of development - blastogenesis - morula
changes to a blastocyst. As the result of the process of cavitation inner cell mass,
embryoblast, is shifted eccentrically, stays attached with trophoblast only on a small range
and projects into the blastocystic cavity. Embryoblast or germinal node gives later rise to
germinal disk, from which the embryonic body will develop. Trophoblast forms the wall of
blastocyst. Cells of trophoblast become flat and so that the wall is very thin.
The shape of blastocyst is different in animal species: in ruminants is highly elongated, in pig
is tube-shaped, in carnivores oval, and blastocyst of rabbit is spherical.
Transport of morula to the uterus takes 3 – 4 days in cow, sheep and cat, 2 – 3 days in sow, 8
– 10 days in mare and bitch. After entrance to the uterus morula occurs in stage of 8 – 16
blastomeres in cow and sheep, usually 16 blastomeres in mare, 4 – 10 blastomeres in sow, in
mice till 32 blastomeres and e.g. in rat in stage of blastocyst.
The growth, expansion and shape of the blastocyst relate to the type of its attachment to the
endometrium and are species specific. Where the blastocyst invades the endometrium, little
expansion is observable (primates, rodents and guinea-pigs). Associated with superficial or
central attachment (horses, dogs, cats and rabbits) there is marked round to oval expansion of
the blastocyst. Obvious thread-like expansion occurs in cattle, sheep and pigs.
20
Figure 5.2 Cleavage of the zygote and formation of the blastocyst.
The period of the morula begins at the 12 to 16 blastomeres. The zona pellucida has disappeared
by the blastocyst stage. Firstly the daughter cells are smaller than the parent cells. Later the zona
pellucida degenerates and the blastocyst enlarges considerably.
21
5.1.2. Gastrulation and notogenesis in mammals
Gastrulation is characterized by the transformation of embryoblast to germinal disk and
differentiation of germ layers, ectoderm and endoderm.
During notogenesis third germ layer mesoderm and chorda dorsalis develop.
5.1.2.1. Formation of germ layers
After the free blastocyst has floated in the uterine secretions for approximately 2 days, the
zona pellucida gradually degenerates and disappears and hatching of the blastocyst can be
observed.
In stage of later blastocyst moving of cells, according to their genetic disposition, to places of
next differentiation realizes. These series of orderly cell migrations lead firstly to origin of the
two flat germinal layers ectoderm and endoderm whereby embryoblast is transformed to the
germinal disc (discus embryonicus). Development of the germinal disc is different in some
carnivores and rodents and ruminants, horse and pig.
 In carnivores and rodents the embryoblast pushes the trophoblast cells from each other,
they subsequently disappear, and the embryoblast bulges above the surface of the
blastocyst. The superficial cells of the embryoblast organize to the flat and form the
ectoderm of the germinal disc. From its bottom part cells organize to the flat as well and
form the layer which lines the blastocyst cavity. This layer is inner germinal layer – the
endoderm. In cranial portion of germ disc the endoderm thicken up to the prechordal
plate.
 In ruminants, horse and pig the germ disk is initially covered by the layer of trophoblastic
cells – Rauber´s layer. Firstly the layer of endodermal cells separates from the bottom
part of the embryoblast, forming the endoderm lining the blastocyst cavity. After that the
cavity forms inside the germinal node – the embryocystis. Cells of its roof penetrate
through the Rauber´s layer on the surface of the blastocyst, make way and the bottom of
the embryocystis ascends above surrounding trophoblast and forms flat layer – the
ectoderm of the germinal disc. (Fig. 5.3)
 In man, primates, bad and hedgehog the germinal disc differentiates by different manner.
Rauber´s layer persists, while in other species it disappears prior implantation. A small
fluid filled intercellular spaces appear (later coalesce) in the germinal node. This space is
the primordium of the amniotic cavity. Cells of the germinal node differentiate to the
amniogenic cells, which separate to form the amnion and to the bilaminar plate of cells,
the germinal disc, consisting of two layers, the epiblast and the hypoblast.
Embryonic ectoderm gives rise to the epidermis, central and peripheral nervous systems, the
eye, inner ear, and, as neural crest cells, to many connective tissues of head.
Embryonic endoderm gives rise to the epithelial linings of the alimentary and respiratory
tracts, including small glands opening into them and the glandular cells of the liver and
pancreas.
5.1.2.2. Primitive streak
Next developmental changes are visible firstly on the surface of germinal disc.
On the caudal portion of germinal disc, axially, a thickened linear band of cells appears – the
primitive streak. It results from the cell proliferation and movement of ectodermal cells to
median plane. Cranial end of the primitive strike terminates in the middle of germinal disk by
cells accumulation – the primitive node (Hensen´s node).
Concurrently, a narrow groove – the primitive groove – develops in the primitive streak, that
is continuous with a small depression in the primitive node – the primitive pit. (Fig. 5.4)
22
2
3
1
A
4
B
5
8
9
6
7
10
7a
11
10
Figure 5.3 The germinal disc formation, the development of ectoderm, endoderm and
the base of mesoderm in ungulate (A) and in carnivores (B).
1 – blastocyst, 2 – embryoblast, 3 - trophoblast, 4 – blastocoele, 5 – endoderm, 6 – the base
of ectoderm, 7 – proliferation of endoderm, 7a – endoderm, 8 – Rauber´s layer, 9 –
embryocystis, 10 – ectoderm of the germinal disc, 11 – the base of mesoderm
23
5.1.2.3. Notochordal process and notochord
Some cells leave the lateral sides and deep surface of the primitive streak and the primitive
node forming the third germinal layer, mesoderm, in form of mesodermal wings. These
wings grow laterally between the embryonic ectoderm and the embryonic endoderm and then
continue outside of the germinal disc, between the trophoblast and endoderm. (Fig. 5.4C)
The cells of the primitive node multiply and this cell mass migrates ventrally an immediately
cranially, forming a median cellular cord between ecto- and endoderm, the notochordal
process. This process soon acquires a lumen by deepening of the primitive pit, the
notochordal canal. The notochordal process grows cranially, until it reaches the prechordal
plate, a small circular area of columnar endodermal cells (endodermal thickening), where
ecto- and endoderm are in contact. (Fig. 5.4B) The prechordal plate later gives rise to the
endoderm of the oropharyngeal membrane located at site of the future oral cavity.
In addition to the mesodermal wings rising from the primitive streak and the primitive node,
next mass of mesoderm grows laterally from the lateroventral sides of the notochordal
process also in form of mesodermal wings. (Fig. 5.6)
Moreover, some mesodermal cells migrate cranially on each side of notochordal process and
around prechordal plate. Here they meet cranially to form cardiogenic plate, from which the
heart primordium begins to develop.
Mesenchyme, or mesenchymal connective tissue, is a type of undifferentiated loose
connective tissue that is derived mostly from mesoderm. The term mesenchyme essentially
refers to the morphology of embryonic cells. Mesenchymal cells can migrate easily, are
amoeboid and actively phagocytic. Mesenchyme is characterized morphologically by a
prominent ground substance matrix containing a loose aggregate of reticular fibrils and
unspecialized cells. Mesenchyme forms the supporting tissue of the embryo.
5.1.2.4. Formation of chorda dorsalis
The notochordal process has an appearance of empty tube, which extends from the primitive
node to the prechordal plate. The floor of the notochordal process gets near and fuses with
underlying endoderm. The fused layers gradually undergo degeneration, resulting in
formation of numerous openings in the floor of the notochordal process. Subsequently, these
openings become confluent and the floor of the notochordal process disappears. In this way
the tube of the notochordal process changes to the notochordal plate. The margins of the
plate curve ventrally, the notochordal cells proliferate, the groove fills by cells and the
notochordal plate infolds. After closing of the groove by fusion of plate margins a compact
chorda dorsalis - notochord is completed. (Fig. 5.5)
The chorda dorsalis presents the first firm axis of the embryo, nevertheless in the next
development it disappears. The reminder of chorda dorsalis persists as nuclei pulposi of
intervertebral discs.
24
Figure 5.4 Development of notochordal process and migration of mesoderm cells.
Dorsal (A), lateral (B), and transversal (C) views of germinal disc showing formation of axial
structures.
25
D
embryonic
ectoderm
neural groove
endoderm
intraembryonic
mesoderm
notochordal canal
notochordal
process
D1
fusion of the floor of the
notochordal process with
the endoderm
D2
desintegration of
fused layers
D3
notochordal plate intercalated
into the endoderm
26
D4
notochordal plate
infolding
D5
notochordal canal
obliteration
D6
notochord detachment
from the endoderm
Figure 5.5 Development of notochord in median plane of the germinal disc by
transformation of the notochordal process. Transversal view of germinal disc at level D
shown in Figure 5.4A.
27
neural groove
ectoderm
endoderm
migrating
mesodermal cells
notochordal process
neural folds
intraembryonic
mesoderm
notochordal plate infolding
28
neural folds
notochord
paraaxial
mesoderm
intraembryonic
coelom
lateral mesoderm
intermediate mesoderm
Figure 5.6 Migration of mesodermal cells from sides of notochordal process. Transversal
sections of the trilaminar embryonic disc at level D shown in Figure 5.4A.
5.1.2.5. Neurulation – formation of the neural tube
During neurulation, the embryo is named neurula.
Above the notochord in median longitudinal axis of the germ, cranially from the primitive
node, ectodermal cells become multiply. This elongated plate of thickened epithelium is
named the neural plate. The neural plate formation is induced by signals from developing
notochord. The neural plate invaginates along its central axis to form a longitudinal median
neural groove, which has neural folds on each side. (Fig. 5.7, Fig. 5.8)) The neural folds
begin to move together and fuse. This conversion of the neural plate to the neural tube, the
primordium of the CNS, starts from central portion and spreads longitudinally to the ends.
Cranially and caudally the neural tube is opened (neuroporus cranialis and neuroporus
caudalis). Caudal opening in some mammals temporarily communicates with umbilical
vesicle by the neurenteric canal (canalis neurentericus).
Cranial opening closes earlier than caudal. Cranial portion of neural tube grows much more
and much faster and lifts up the surface of germinal disc. This portion presents the base of the
brain, remaining part gives rise to the spinal cord.
The neural tube soon separates from the surface ectoderm (non-neural ectoderm) as the neural
folds meet and the free edges of the surface ectoderm fuse, so that the surface ectoderm
becomes continuous over the neural tube. Subsequently the surface ectoderm differentiates
into the epidermis.
29
5.1.2.6. Neural crest formation
As the neural folds fuse to form the neural tube, some neuroectodermal cells lying along the
inner margin of each neural fold give rise to the neural crest. (Fig. 5.7) The neural crest
separates from the margins and after the neural tube separates from the surface ectoderm,
forms a flattened mass between the neural tube and the overlying surface ectoderm. The
neural crest soon separates to right and left parts, which are located bilaterally alongside
dorsolateral part of the neural tube. After transversal separation to the groups of cells,
ganglions of brain nerves (V, VII, IX, X) arise from cranial portion and spinal ganglions from
the caudal portion. In addition migrating neural crest cells form the neurolemma (Schwan
sheet) of peripheral nerves, contribute to the formation of leptomeninges (pia mater and
arachnoid), to the formation of suprarenal (adrenal) medulla, pigment cells and some
connective tissues of head.
Figure 5.7 Neurulation
and development of the
neural crest.
1 - surface ectoderm
2 - neural plate edges
3 – neural plate
4 - notochord
5 - neural folds
6 - neural groove
7 - neural crest
8 - neural tube
9 - developing
spinal ganglion
30
1
2
4
10
3
8
9
9
6
6
5
10
10
7
7
Figure 5.8 Development of the neural tube. 1 - surface ectoderm, 2 - neural plate, 3 neural folds, 4 - neural groove, 5 - neural tube, 6 - cranial neuropore, 7 - caudal neuropore, 8 primitive node, 9 - primitive streak, 10 – somites. Modified from Hyttel et al. (2010).
31
5.1.2.7. Mesoderm formation
By the development of mesoderm the notogenesis (formation of organs) begins.
Mesoderm develops from the primitive streak, the primitive node and the notochord, so called
axial structures of the germinal disc, in form of mesodermal wings, which grow laterally
between ectoderm and endoderm (Fig. 5.6) and then continue outside of germinal disc,
between trophoblast and endoderm.
The portion of the wing near by the axis is named the paraxial plate (paraxial mesoderm),
neighbouring middle portion of the wing is named intermediate plate (intermediate
mesoderm) or urogenital plate and the most laterally is the lateral plate (lateral mesoderm),
which is continuous with the extraembryonic mesoderm covering the umbilical vesicle and
amnion.
The paraxial and urogenital plates undergo segmentation.
The paraxial plate condenses, differentiates and by transversally oriented incisions is divided
to cuboidal accumulations of cells, the somites (soma = body), arranged in craniocaudal
sequence on either side of developing neural tube. (Fig. 5.8) The somites form distinct surface
elevations on the embryo.
Laterally, intermediate (urogenital) plate undergoes segmentation as well, and individual
cell groups create from somites laterally emanating stems. These stems present the bases of
urinary system and due to this are termed nephrotomes. From nephrotomes a pronephros and
mesonephros develop.
The lateral plate does not undergo segmentation. It delaminates to two layers, referred to as a
splanchnopleura and somatopleura. The splanchnopleura (visceral layer) is located
adjacent to the endoderm; the somatopleura (parietal layer) is located beneath the ectodermal
epithelium. Between them firstly isolated coelomic spaces appear, which soon coalesce to
form a single horseshoe-shaped cavity, the intraembryonic coelom (Fig.5.6). During next
development this intraembryonic coelom is divided into three body cavities - peritoneal,
pericardial, and pleural.
Cranial portion of mesoderm, ahead of notochord, cardiogenic plate, also does not undergo
segmentation.
5.1.2.8. Development of somites
The somites of paraxial mesodermal plate undergo the next development.
The cells of somite space out and the small cavity, myocel, rises inside.
Ventromedial part of the somite, sclerotome, changes to the mass of mesenchymal cells,
which move to the necessity of the nerve tube and chorda dorsalis and create here the base of
vertebrae and other axial skeleton. From the dorsal part of the somite two plates arise,
myotome and dermatome. (Fig.5.9) The myotome gives rise to skeletal muscle and from the
dermatome the corium and subcutis develop.
The first pair of somites appears in a short distance caudal to the site at which the otic placode
forms. Subsequent pairs form in a craniocaudal sequence. Cranial somites are older than
caudal. From the second to the fourth week of gestation in domestic animals, somites may be
observed beneath the surface ectoderm as paired structures on either side of the neural tube.
Thus, the approximate age of embryo can be estimated according to the number of pairs of
somites.
Derivatives of individual somite pairs are called metameres and the whole phenomenon is
metamerism. In vertebrate metamerism is observable only during development, in adults is
obscure. In invertebrates (worms) is metamerism observable for all the life and due to creation
of new metameres the body elongates.
32
3
4
5
1
2
6
7
5a
8
9
8
10
Figure 5.9 Differentiation of the somites. 1 - ectoderm, 2 – endoderm, 3 – neural tube, 4 –
neural crest, 5 – somite, 5a – derma-myotome, 6 – myocel, 7 – notochord, 8 - cells of
sclerotome, 9 – dermatome, 10 - myotome
33
5.2. Blastogenesis in birds
5.2.1. Cleavage and blastulation in birds
As mentioned above, eggs of birds are polylecithal. The yolk globe is typical by large
accumulation of yolk. The yolk inclusions are accumulated especially at the vegetative pole,
whereas at the animal pole prevails the cytoplasm (anisolecithal egg). In consequence of it,
cleavage and germ development only at the animal pole proceeds, within the range of small
area. This manner of cleavage is partial discoid.
The first two meridional grooves appear in the centrum of disc, forming 4 blastomeres, only
partially separated from one another. The next 2 grooves cross one previous, so 8 blastomeres
rise. Following groove is circular and demarcates middle portion of cells, which are smaller
and completely defined. At the periphery the cells are flattened, larger in surface extent, and
are not walled off from the yolk beneath. During the next cell division disc-shaped morula
arises, separated from the upper side of the yolk by the subgerminal cavity. (Fig. 5.10A)
Based on agile mitotic division, the disc becomes two-layer and soon multi-layer. In the stage
of 64 blastomeres cells space out and the circular, horizontally oriented cavity, the
blastocoele, rises inside. The superior layer, the epiblast, is originally a single layer of
blastomeres, which multiply and form the germinal disc. Later, the germinal disc
differentiates to germinal layers - the ectoderm endoderm and mesoderm. The bottom of the
blastocoele, the hypoblast, consists of blastomeres some of which are still connected with the
yolk. The hypoblast is destined to become the extra-embryonic endoderm. This formation
corresponds to blastula of lower vertebrate. Owing to its shape the term discoblastula is used.
At the circumference of the discoblastula, the epiblast and hypoblast coalesce, forming multilayer germinal circumvallation.
Central portion of the germinal disc above the blastocoele becomes thinner and paler - area
pellucida, peripheral part is darker, thicker, and is named area opaca. Externally from the
germinal disc the yolk globe is not cleaved. It is named area vitellina.
5.2.2. Gastrulation and notogenesis in birds
During gastrulation the germinal disc differentiates not only to proper germ, but also to
embryonic appendages, which serve to the protection and the nutrition of the developing
germ.
Initially, the germ disc is circular. Owing to the cell multiplication it becomes multi-layer and
pear-shaped (observable from above). Soon the germ disc delaminates to superficial cell
layer, the base of ectoderm, and deep layer of flat cells, the base of endoderm. The
endoderm in cranial portion of the germinal disc becomes thicken, forming the prechordal
plate.
In middle line the ectoderm of the germinal disc starts to proliferate and forms ridge-like
thickening, extending from the caudal inner margin of area opaca to approximately the centre
of area pellucida. This primitive streak lies in the longitudinal axis of the future embryo. The
end adjacent to area opaca is its posterior (caudal) end; the opposite extremity is its anterior
(cephalic) end. The anterior end extends to the primitive node (Hensen´s node).
Simultaneously with forming of these structures the primitive groove develops in the
primitive streak and the primitive pit in the primitive node. The primitive streak functions
like the foundation of mesoderm, which expands laterally between ectoderm and endoderm.
The cells of the Hensen´s node multiply; mass of cells migrates cranially, forming a median
cellular cord between ecto- and endoderm, the notochordal process. Inside, the notochordal
34
canal rises by deepening of the primitive pit. The notochord provides material for forming of
chorda dorsalis. Moreover, from the lateral sides of the notochord, mesoderm in form of
mesodermal plates grows laterally. Some mesodermal cells originating from cranial portion of
the mesoderm move cranially and ahead of the notochord giving rise to the cardiogenic plate.
A
blastodisc
area opaca
blastomeres
area pellucida
blastomeres
B
blastocoele
blastoderm
area opaca
epiblast
blastomeres
hypoblast
area vitellina
sub-germinal cavity
Figure 5.10 Stages of cleavage in the avian zygote, formation of blastoderm.
A – blastodisc from above, B – blastodisc in cross-section
35
Paraxial mesodermal plate, laying near the chorda dorsalis, forms pairs of somites. At this
time birds germ is 24 hours old. Segmentation continues, one segment per hour, until 48
hours.
Urogenital mesodermal plate, located laterally from previous, organises to stems connecting
somites with non-segmented lateral mesodermal plate. The stems differentiate to
nephrotomes, giving rise to organs of the urinary system.
Lateral mesodermal plate, remaining part of mesoderm, delaminates to parietal and visceral
layer, the somatopleura and splanchnopleura. The space between them is body cavity, the
coelom.
The somatopleura and the splanchnopleure extend ventrally around the yolk globe, between
ectoderm and endoderm, and there, in middle line they join. In this way, the body cavity,
consisting of embryonic and extra embryonic coelom is established.
The next development of somites is similar to that in mammals. Dorsolateral part of somite,
the dermatome, gives rise to the corium of the skin. Medial part, positioned next to the neural
tube and the chorda dorsalis, the sclerotome, presents the foundation of vertebrae and ribs. In
addition, the sclerotome provides the material for formation of mesenchyme. Ventrolateral
part of somite, the myotome, gives rise to striated skeletal muscle of the body and limbs.
The process of neurulation and the neural crest development is the same like in mammals.
The endoderm in range of germinal disc differentiates to the archenteron – primitive gut
cavity, lying axially longitudinally.
36
6 FETAL MEMBRANES AND EXTRAEMBRYONIC ORGANS
6.1. Foetal membranes and extraembryonic organs in mammals
The origination of foetal membranes and extraembryonic organs is conditioned by the stage of
phylogenetic development. In lower animals, the egg is coated by secondary envelopes,
protecting against external environment influences. For example in amphibians and fish, there
is gelatinous capsule protecting the egg before dehydration. The next development continues
in water.
In higher animals, amniote vertebrates (reptiles, birds and mammals), the germs of which are
exacting on sustenance and the removal of waste products of metabolism, foetal membranes
and accessory embryonic organs were created.
The function of them is protection of embryo, securing of water environment, sufficient
supply of nutrients and the removal of waste products.
The embryos of reptiles, birds, and mammals produce 4 foetal membranes:
 amnion
 yolk sac
 chorion, and
 allantois
In birds and most reptiles, the embryo with its foetal membranes develops within a shelled
egg.
 The amnion protects the embryo in a sac filled with amniotic fluid
 The yolk sac contains yolk – the only one source of food until hatching. Yolk is a
mixture of proteins and lipoproteins.
 The chorion lines the inner surface of the shell (which is permeable to gases) and
participates in the exchange of O2 and CO2 between the embryo and the outside air.
 The allantois stores metabolic wastes (chiefly uric acid) of the embryo and, as it
grows larger, also participates in gas exchange.
Although (most) mammals do not make a shelled egg, they do also enclose their embryo in an
amnion. For this reason, the reptiles, birds and mammals are collectively referred to as the
amniota.
In placental mammals, the extraembryonic organs, placenta and umbilical cord, form and
connect the embryo to the mother's uterus in a more elaborate and efficient way. The blood
supply of the developing foetus is continuous with that of the placenta. The placenta extracts
food and oxygen from the uterus. Carbon dioxide and other waste (e.g. urea) are transferred to
the mother for disposal by her excretory organs.
6.1.1. Yolk sac (saccus vitellinus)
The yolk sac differentiates in the stage of the blastocyst, which is enclosed within the zona
pellucida and consists of an inner cell mass and a layer of trophoblastic cells. Embryonic
ectoderm of the germinal disc transitions on its periphery to trophoblast (extraembryonic
ectoderm). As gastrulation proceeds endodermal cells separate from the embryonic disc and
line the blastocyst cavity leading to formation of bilaminar yolk sac. (Fig. 6.1A) Embryonic
37
mesoderm, which occupies a position between the inner endodermal layer and the outer
trophoblastic layer, transitions to extraembryonic forming the trilaminar yolk sac. (Fig. 6.1B)
embryonic disc
A
B
ectoderm
mesoderm
endoderm
bilaminar yolk sac
amnionic
folds
trilaminar yolk sac
amnionic
folds
splanchnopleure
gut
final
yolk
sac
somatopleure
C
extraembryonic
coelom
D
Figure 6.1 The yolk sac development in domestic animals. A – bilaminar yolk sac, B –
trilaminar yolk sac, C – formation of the somatopleura and splanchnopleura, D – growth of
amniotic folds and formation of definitive yolk sac
38
The mesoderm of the trilaminar yolk sac gradually splits into an outer somatic and inner
splanchnic layer, the somatopleura and splanchnopleura (Fig. 6.1D), which line the coelom
cavity.
The germinal disc becomes to separate from extraembryonic portion of blastocyst by firstly
cranial and caudal groove, subsequently lateral grooves. Simultaneously the process of
folding of the embryo begins. Folding occurs in both the median and horizontal planes and
results from rapid growth of the embryo. The grooves interconnect to the circular groove,
which penetrates deeper to the mesoderm and endoderm. The blastocystic cavity lined with
endoderm, owing to this constriction, divides to the dorsal portion (archenteron, primitive gut)
and the ventral portion, the yolk sac (vitelline sac, umbilical vesicle. (Fig. 6.1D) Both portions
communicate mutually by the ductus omphaloentericus. To the endoderm of the yolk sac the
splanchnopleure (the extraembryonic mesoderm) is attached.
Within this layer of extraembryonic mesoderm of the yolk sac and umbilical cord,
angiogenesis or blood vessels formation begins. Mesodermal cells multiplicate and form the
mesenchyme (mesoderm derived primitive tissue). Mesenchymal cells differentiate into
angioblasts (vessel forming cells). Angioblasts aggregate to form clusters, called blood
islands, from which both, endothelial cells of blood vessels and primitive blood cells develop.
Small spaces appear within the blood islands and they later fuse. From the angioblasts, lining
of the inner surface of blood vessels develops (endothelium) and some of them give rise to
haemoblasts, primitive blood cells.
By mutual connection of the blood vessels bases, two veins, venae omphalomesentericae
create, which lead the blood within the wall of the yolk sac towards the heart primordium.
Concurrently, the heart and big vessels create from the mesoderm of the cardiogenic
plate. Paired, longitudinal endothelium-lined channels, the endocardial heart tubes, develop
and fuse to form a primordial heart tube.
By this way the first, so called vitelline blood circuit is created. In mammal it is not
by far so important like in birds.
The size and function of the yolk sac differs in mammal species. Its functional exercise is
given first of all by the connection with chorion. It is observable e.g. in the horse, where the
splanchnopleura of the yolk sac wall attaches to the somatopleura and they grow together.
Into this mesodermal layer blood vessels penetrate. After connection with endometrium of the
uterus the primitive placenta, yolk sac placenta (omphaloplacenta) rises. The yolk sac
placenta is important only in early pregnancy (till 14th week of the pregnancy). Similarly the
yolk sac placenta occurs in marsupials.
6.1.2. Amnion and chorion
The amnion and chorion develop in mammals by the different manner. In domestic animals
the development is similar like in other amniota, birds and reptiles.
Fetal membranes, the amnion and chorion, start to develop at the stage of germ disc
differentiation, when cranial, caudal and lateral surrounding grooves are formed and they fuse
to the one circumferential groove. Concurrently the folding of the germ occurs in both the
median and horizontal planes. Extraembryonic ectoderm rather lifts up above the level of
germ disc surface and forms the amniotic folds. The amniotic folds are in fact the duplicatures
of trophoblast (extraembryonic ectoderm) and extraembryonic somatopleura. Subsequently
they grow up, like the roof above the germ. Inner surface of the amniotic fold, turned towards
the germ is amniogenic side and outer surface is choriogenic side. (Fig. 6.2) By this growth,
an opening above the germ becomes smaller and smaller, the folds touch together and
amniotic suture is formed. Due to the suture breaks double layered coat of the germ is
39
created. The inner coat is the amnion and the outer coat is the chorion. The amnion formed
by this manner is termed the pleuramnion.
In higher primates, humans, hedgehog and bat, the amnion forms by the different manner, by
the cavitation. The amniotic cavity differentiates by the separation of embryoblast cells. The
floor of amniotic cavity is formed by the epiblast, future ectoderm of the germ disc and the
roof by amniogenic cells (amnion-forming) – amnioblasts. This type of amnion is termed
schizamnion.
The type of amnion formation influences the type of implantation. Early implantation is
associated with cavitation amniogenesis and late implantation with formation of the amnion
by folding.
Outer coat of the germ is the chorion. Both foetal membranes consist of trophoblast and the
extraembryonic somatopleura, naturally to the amnion attached externally and to the chorion
from the inside.
Soon amnioblasts start to produce amniotic fluid.
Owing to elongation of the germ body and the development of some organs at the
head and tail end, the endodermal cavity strangulates and divides to the gut and the yolk sac
(umbilical vesicle). Originally wide communication of both narrows to the narrow tube
(ductus omphaloentericus). At this point the endoderm of the yolk sac transitions to the
endoderm of the gut (gut umbilicus) and the ectoderm of the germ body transitions to the
extraembryonic ectoderm of the amnion (skin umbilicus). Longitudinally, by the narrowing of
the gut-yolk sac connection the foregut and hindgut are created. The midgut stays ventrally
connected with the yolk sac, which in mammals does not undergo next development. (Fig.
6.3) The rudiment of the embryonic yolk sac is designated "Meckel's diverticulum“.
1
6
6
6
6
6a
6b
2
2
9
3
3
4
7
10
4
5
7
8
5
Figure 6.2 The arrangement of the foetal membranes in domestic animals in early (A)
and later (B) gestation on the transversal section. 1 - neural tube, 2 - primitive gut, 3 ductus omphaloentericus, 4 - yolk sac, 5 - exocoelom, 6 - amniotic fold composed of
extraembryonic ectoderm and somatopleura, 6a - its amniotic side, 6b - its chorionic side, 7 wall of yolk sac, 8 - wall of chorion, 9 - body wall of embryo, 10 – umbilicus. Modified from
Horký et al. (1984).
40
A
1
3
2
1
4
5
B
6
1
1
2
3
4
7
5
C
9
10
6
8
4
6
11
7
12
Figure 6.3 The arrangement of the foetal membranes in domestic animals in early
gestation on the longitudinal section:
1 - amniotic fold, 2 - foregut, 3 - hindgut, 4 - future ductus omphaloentericus, 5 - skin
umbilicus, 6 - yolk sac, 7 - allantois, 8 - yolk placenta, 9 - amniotic suture, 10 - amniotic
cavity, 11 - allantochorion, 12 - allantochorionic villi. Modified from Horký et al. (1984).
41
6.1.3. Allantois
Allantois, a sac-like structure is primarily involved in nutrition and excretion and is webbed
with blood vessels. The function of the allantois is to vascularise the chorion so that the
chorioallantoic placenta provides collection of liquid waste from the embryo, as well as
exchange of gases used by the embryo.
The allantois develops early after forming of the hindgut like its evagination consisting of the
endoderm and the splanchnopleure. This evagination directs towards gut umbilicus and
alongside ductus omphaloentericus penetrates into the chorionic cavity (extraembryonic
coelom). The connection of the hindgut and allantois is so called ductus allantoideus, which
is going to be a component of umbilical cord. Later, after horizontal partition of the cloaca to
upper gut and lower urogenital part it will be named urachus.
Owing to considerable enlarging of the allantois cavity, the allantois attaches to chorion and
its splanchnopleure grows together with the chorionic somatopleura (allantochorion).
Additionally the allantois can join with the amnion too, forming the allantoamnion.
The range of this coalescence is very different in mammal species.
In horse and dog, where the yolk sac persists considerably long time, the allantois completely
envelops the amnion so the germ is positioned inside two cavities – amniotic and allantoic.
In ruminants and pig, the yolk sac becomes extinct earlier, the allantois envelops the amnion
only partially and the germ is positioned only in one cavity – amniotic. (Fig. 6.4, Fig. 6.5)
In man, the allantois is only vestigial; the amniotic cavity widely enlarges and joins with the
chorion, forming commonly amniochorion (so that the extraembryonic coelom disappears).
From the base of aorta, two arteriae umbilicales penetrate within the wall of the ductus
allantoideus into the wall of the allantoic sac, abundantly ramify and form extensive capillary
networks, which grow into the chorionic villi. From the venous bed, the two venae
umbilicales form and they run back, again within the wall of the ductus allantoideus, into the
germ, where they enter its blood circuit. This type of the blood circuit is named the
umbilical or placental.
The umbilical circuit replaces the previous form, vitelline blood circuit.
The umbilical cord (funiculus umbilicalis) is the connecting cord from the developing
embryo or foetus to the placenta. On the surface it is covered with the ectoderm and inside,
there are the two umbilical arteries and one umbilical vein (the second obliterates), buried
within Wharton´s jelly (gelatinous connective tissue). The umbilical vein supplies the foetus
with oxygenated, nutrient - rich blood from the placenta. The umbilical cord length may be
different in various animals. In horse and dog it presents about a half of the body length, in
ruminants and sheep about a quarter of the body length, in pig is the longest (comparable with
the body length) and in man it is the double of the body length.
42
10
20
11
2
1
3
12
21
4
18
16 8
7
9
5
6
13
17
15
14
19
Figure 6.4 The arrangement of foetal membranes of mammals in later stage of
development on the longitudinal section. 1 - basis of brain, 2 - neural tube, 3 - primitive gut,
4 - pharyngeal membrane, 5 - cloaca, 6 - cloacal membrane, 7 - basis of heart, 8 - ductus
omphaloentericus, 9 - ductus allantoideus, 10 - amnion, 11 - amniotic cavity, 12 allantoamnion, 13 - allantochorionic wall with chorionic villi, 14 - allantois, 15 - umbilicus,
16 - endocoelom, 17 - exocoelom, 18 - chorion, 19 - yolk sac, 20 - somatopleura, 21 –
splanchnopleura. Modified from Horký et al. (1984).
43
A
ductus
allantoideus
amniochorion
chorion
amnionic cavity
6
allantochorion
residue of yolk sac
allantoic cavity
6 – umbilical cord
B
amnionic cavity
chorion
6
allantochorion
ductus
allantoideus
allantoic cavity
yolk sac
Figure 6.5 Arrangement of the foetal membranes in ruminants (A) and horse (B).
6 – umbilical cord
44
6.2. Foetal membranes in birds
In the higher vertebrate, including birds, 4 foetal membranes develop – amnion, chorion,
yolk sac and allantois.
The functions of them are: protection of the germ, nutrition assurance, exchange of gases, and
excretion of waste products.
6.2.1. The yolk sac development
As mentioned above, originally, the flat germ disc is placed superficially at the animal pole of
the yolk globe. It expands in flat, the central portion becomes thinner - area pellucida and the
peripheral is thicker and darker - area opaca. Around the germinal disc, there is non-cleaved
surface of the yolk globe, area vitellina. Towards the end of gastrulation, the ectoderm
spreads peripherally from the area opaca over the yolk mass. Endoderm forms beneath the
ectoderm, and the bilaminar layer advances beyond the area from which the embryo develops.
Subsequently, the mesoderm develops from the axial structures of the germinal disc, extends
between the ectoderm and endoderm and differentiates to paraxial, urogenital and lateral
plate. Thus a trilaminar layer, the trilaminar yolk sac is established. (Fig. 6.6) The lateral
mesodermal plate splits into an outer avascular somatopleura layer and an inner vascular
splanchnopleura layer which is in contact with the yolk. Segregation of the somatopleura and
splanchnopleura results in formation of the coelom. After the cranial, caudal and lateral
grooves forming and their fusion, the germ separates by the circumferential groove from the
extraembryonic portion and owing to the rapid growth it elevates above the surroundings. The
grooves deepen and trench to the somatopleura, splanchnopleura and endoderm. In this way,
so far integral cavity of the yolk globe separates to upper or dorsal portion – the primitive gut
(archenteron) and lower or ventral portion – the yolk sac. The archenteron consists of cranial
portion - the foregut, middle portion - the midgut and caudal portion – the hindgut. The
midgut communicates with the yolk sac firstly widely, but later this communication becomes
narrower and is termed the yolk stalk (ductus omphaloentericus).
After the fusion of the yolk sac endoderm with the layer of visceral mesoderm
(splanchnopleure), mesodermal cells start to multiply (form mesenchyme) and differentiate.
Newly forming cells accumulate to blood islands and differentiate to the angioblasts and
haemoblasts (angioblasts give rise to endothelium and haemoblasts to primitive blood cells).
The small spaces, which developed inside the islands, fuse to tubular cavities. After the fusion
of these blood vessel bases, two venae omphalomesentericae develop. They lead the
nutritional blood to the germinal blood circuit and conversely deoxygenated blood runs
through two arteriae omphalomesentericae back to the yolk sac. Concurrently with the germ
growth, blood vessels from the surface of the yolk globe deepen and so the resorption area
increases. The resorption through the yolk sac endoderm proceeds. For the better resorption,
the endoderm creates villi-like protrusions penetrating to the yolk, into which splanchnopleura
with capillaries penetrate. In addition, this vitelline blood circuit assures the gases exchange
during the first days of development.
This level of the blood circuit development is observable in birds after 40-hour incubation.
Within the wall of vitelline blood vessels and inside above mentioned endodermal
villi-like protrusions, especially inside the central mesoderm of splanchnopleure, stem cells
develop. Firstly, the stem cells of lymphocytes, which than migrate to the bursa Fabricii and
thymus, secondly the stem cells of erythrocytes, which subsequently colonize the liver and
spleen. After the hatching the yolk sac is retracted into the body cavity and the reminder of
the yolk inclusions serves about one day like the source of nutrition.
45
embryo
amnionic fold
ectoderm
air sac
endoderm
splanchnopleure
somatopleure
shell
membrane
coelom
trilaminar
yolk sac
blood
vessels
bilaminar
yolk sac
albumen
mesoderm
yolk
shell
Figure 6.6 Chick embryo - formation of the trilaminar yolk sac. Separation of
extraembryonic mesoderm into splanchnic and somatic layer
6.2.2. Amnion and chorion
Amnion and chorion in birds develop by the same manner like in mammals.
Extraembryonic ectoderm in conjunction with the somatopleura forms folds (cranial, caudal
and lateral), which elevate above the surface of the germ. The cranial fold grows faster than
others and all folds meet together above the caudal portion of the germ. The place, where they
grow together, is the amniotic suture. The side of the fold turned towards the germ is the
amniotic side; the side turned externally is the chorionic side. Due to the suture break double
layered coat of the germ is created. Inner coat is the amnion and outer coat is the chorion.
(Fig. 6.7)
Consequently, the amniotic cavity (cavum amnii) fills with amniotic fluid (liquor amnii). At
first it is mainly water with electrolytes, but about the 12 - 14th week the liquid also contains
proteins, carbohydrates, lipids, phospholipids and urea, all of which aid in the growth of the
foetus. The amniotic fluid establishes favourable environment for the germ and protects it
against the mechanical insult.
The chorion envelopes completely all the germ with its amnion and yolk sac and is separated
from them by the exocoelom. Externally, the layer of egg white is attached to the chorion.
6.2.3. Allantois
In the stage about 28 somites, allantois develops as an outgrowth of the ventral portion of
hindgut, consisting of the endoderm and splanchnopleure. Firstly small evagination grows
alongside the yolk stalk (ductus omphaloentericus) towards the extraembryonic coelom,
46
where expands to the spacious sac. The connection of the allantois with the hindgut is named
vitello-intestinal duct - ductus allantoideus. (Fig. 6.7)
Enlarging of the allantois depends on the urine volume. The urine is produced by
primitive urinary system, mesonephros, and by the mesonephric duct (also called the Wolffian
duct) is transported to the common cavity into which the intestinal, genital, and urinary tracts
open - cloaca (its part urodeum). The allantois enlarges rapidly, the 5 – 6th day of the germ
development it surrounds amnion, till 8th day nearly all the yolk sac and the 12th day it
surrounds the entire embryo and both ventral ends fuse. By the fusion with external foetal
membrane, chorion, the uniform membrane - allantochorion is created. The allantochorion
covers all the inner surface of the egg shell, absorbs oxygen through the porous shell from the
atmosphere for nourishment of the embryo and it also discharges waste carbon dioxide
through the shell.
Two aortic branches, arteriae umbilicales, penetrate through the ductus allantoideus
and within the allantoic wall form rich networks of capillaries. Backwards, two venae
umbilicales lead nutritional blood to the germ body. By this way, the second, umbilical
blood circuit is established. So the germ obtains the possibility of the nutrition by resorption
of the egg white. After it, since 16th day, the nutrients are obtained again from the egg yolk.
Moreover, the umbilical blood circuit enables the germ respiration, because allantochorion is
attached tightly to the perforated, oxygen-permeable egg shell. The vicinity of the rich
capillary network and the egg shell also enables the resorption of the calcium ions.
amnion
amnionic
cavity
shell
shell
membrane
allantoamnion
air sac
allantoic
cavity
somatopleure
splanchnopleure
vitellointestinal
duct
chorion
allantochorion
albumen
yolk sac
Figure 6.7 Foetal membranes of the chick embryo. Enlargement of the allantois between
the chorion and amnion.
47
7 IMPLANTATION OF THE GERM
The implantation of the germ is the process in which the fertilized egg embeds itself in
the wall of the uterus.
The fertilized egg undergoes cleavage, descends along the oviduct and enters the
uterus. The time of the descensus may be different, varies 3 – 8 days in animals. At this stage,
dividing egg consists of 8 – 16 cells and is surrounded with zona pellucida. Later the
multicellular morula changes to the blastocyst and after shedding the zona pellucida, the
blastocyst becomes implantation competent. This preimplantation stage varies in duration
between species. In rabbit and mice, implantation occurs 4 days post coitum, in humans
average 9 days, in cows implantation does not occur until 30 days, in others large domestic
animals 30 – 60 days and in wild animals sometimes several months.
An intimate cross-talk between the embryo and the uterus is needed for blastocyst
implantation. This process, which consists of an interaction between trophoblast cells and
endometrium, can only take place in a restricted period of time, termed "window of
receptivity". It is initially dependent upon the presence of estrogen and progesterone,
although further morphological and biochemical changes are evoked within the uterine wall
by signals from the embryo and invading trophoblast. Indeed, out of this period the epithelium
apical surface is covered by a thick glycocalyx, which prevents blastocyst attachment.
On reaching the uterus, the blastocyst hatches from the zona pellucida and remains free for a
short time in the uterine lumen. During this period, it receives nourishment from secretions of
the uterine glands.
The site of implantation is different in the individual animal species. In sheep and cow
the germ implants in the inferior part of uterus, rather at the side of ovulation. In horse the
germ sometimes moves to opposite cornu uteri. In pig, dog and cat implanted germs dispose
regularly and their partial separation is assured by forming of mucosal folds between them.
Indeed, generally is valid, that the rule for distribution of germs in the uterus doesn’t exist.
The endometrium is ready for the implantation entirely and the germ may be implanted
anywhere.
The form of implantation according to the penetration depth into the endometrium
differs from one species to another.
Central, eccentric and interstitial implantations are distinguished. (Fig. 7.1)
Central implantation – the germ is located in the uterine cavity and fluid-filled sacs
surrounding the embryo expand so that the extra-embryonic membranes become apposed to
the uterine epithelium and attach to it by chorionic villi (ungulate, carnivores).
Eccentric implantation - the embedding of the germ within a folds or recesses of the
uterine mucosa, which then closes off from the main cavity (rodents).
Interstitial implantation - the complete embedding of the blastocyst within the
endometrium of the uterine wall. The germ develops inside the uterine wall cavity, exactly
separated from the uterine lumen (human, primates, guinea pig, and hedgehog).
In interstitial and eccentric implantation, the site of blastocyst attachment is described by
relating its position in the uterus to the mesometrium. When the blastocyst implants at the
same side as the attachment of the mesometrium, this is referred to as mesometrial
implantation. (Fig. 7.1 A1) When implantation occurs at a site opposite to the attachment of
the mesometrium, this is referred to as anti-mesometrial implantation. (Fig. 7.1 A2) The
orientation of the blastocyst is also described by relating the position of the inner cell mass to
the mesometrium. (Fig. 7.1 C1, C2)
48
1
A1
A2
2
7
3
5
4
6
Figure 7.1 Forms of implantation.
B
A1 – intersticial mesometrial
A2 – intersticial anti-mesometrial
B – eccentric antimesometrial implantation
C1 – centric with mesometrial position of
the inner cell mass
C2 - centric with anti-mesometrial position
of the inner cell mass
1 - mesometrium, 2 – uterine mucosa,
3 – uterine lumen, 4 – inner cell mass,
5 – trophoblast, 6 – blastocyst cavity,
7 – uterine muscle wall
2
3
C1
C2
7
3
4
49
8 PLACENTA AND TYPES OF PLACENTA
After entering the uterine cavity, the embryo is firstly nourished by secretions from the
uterine glands – histiotrophe. During the next development, this way of nutrition becomes
insufficient and has to be replaced by the anatomic arrangement, which facilitates import of
nutrients and export of waste products through the maternal circulatory system –
haemotrophe.
The placenta is an organ characteristic of placental mammals during pregnancy,
joining mother and offspring, providing endocrine secretion and selective exchange of
soluble blood borne substances through apposition of uterine and trophoblastic vascularized
parts.
 endocrine secretion - the placenta secretes both estrogens and progesterone.
 selective exchange - diffusion of nutrients and oxygen from the mother's blood into the
foetus’s blood and diffusion of waste products and carbon dioxide from the foetus back to
the mother. This two-way exchange takes place across the placental membrane, which is
semipermeable; that is why it acts as a selective filter, allowing some materials to pass
through and holding back others.
In placental mammals, the placenta forms after the embryo implants into the wall of the
uterus. The developing foetus is connected to it via an umbilical cord.
Domestic animals have a chorioallantoic placenta in which the outer layer of the allantois is
fused with the inner layer of chorion and the foetal umbilical vessels are distributed in the
primitive connective tissue (= mesenchyme, rising by fusion of splanchnopleura and
somatopleura) between those two.
The placenta of domestic animals is created by differently extensive and differently
intimate connection of the chorion (allantochorion) with the uterine mucosa (endometrium).
Chorionic part is named pars foetalis and the endometrium in the range of future placenta
pars materna.
In mammals, during the phylogenetic development originate several types of placentae, which
differ by:
1) the arrangement of chorionic villi
2) the intimacy of connection (the number of layers, which separate the mother blood
from the foetal blood - so called placental barrier)
ad 1)
Chorionic villi originally develop throughout all the surface of allantochorion, but later they
partially disappear. The chorion with villi is termed chorion frondosum; the portion of the
chorion without villi is chorion leave.
According to the arrangement of the chorion frondosum 4 types of placentae are classified:
Placenta diffusa - the villi on the foetal chorion are distributed over the entire placenta as in
mares and sows (Fig. 8.2; Fig. 8.3)
Placenta cotyledonata - distribution of the villi on the foetal chorion is localized in multiple
circumscribed areas—the cotyledons (ruminants) (Fig. 8.4)
Placenta zonaria – type of placenta in which the chorionic villi are restricted to an equatorial
girdle, as in the bitch and cat (carnivores) (Fig. 8.5)
Placenta discoidea - a placenta in which the chorionic villi are arranged in a circular plate as
in human, primates, rodents and bat placentae. (Fig. 8.6)
50
Ad 2)
Animal placentae are classified according to the number of tissue layers separating the
maternal and foetal circulations. In time of the placental development, both parts, pars foetalis
and pars materna consist of 3 layers, so that placental barrier is 6 layered:
Pars foetalis
 endothelium of the chorionic blood vessels
 chorioallantoic mesenchyme
 superficial epithelium on the surface of the chorionic villi
Pars materna
 uterine epithelium
 mucosal connective tissue (lamina propria mucosae)
 endothelium of the capillaries
Some layers of especially pars materna, mentioned above, may be fermented by the lytic
action of the resorptive epithelium of chorionic villi and so the chorionic villi penetrate
deeper. By this way the connection of pars materna and pars foetalis becomes more intimate.
Depending on this intimacy of connection, the uterine mucosa is lost when the pregnancy
terminates or not. In non-deciduate placenta (semiplacenta, placenta apposita), no
maternal tissue is lost when the pregnancy terminates. Deciduate placenta is a placenta or
type of placentation in which the decidua or maternal parts of the placenta separate from the
uterus and are cast off together with the trophoblastic parts. Endometrial blood vessels are
damaged and physiological bleeding come on.
The placentation types (Fig. 8.1) found in animals are:
a) epitheliochorial placenta (placenta epitheliochorialis)
- the epithelium of the uterus and the chorion are in contact in this placentation, but there is no
erosion of the epithelium. Characteristic of sows and mares. Called also adeciduate placenta.
In the horse, the yolk sac is initially a prominent structure, which together with chorion forms
choriovitelline placenta providing the basis for foetal-maternal exchange. Later the yolk sac
involutes, and a chorioallantoic placenta takes over the function for the rest of pregnancy.
b) cotyledonary placenta (placenta cotyledonata or multiplex)
- presents the transitional type between the adecidual and decidual placenta (so called
semiplacenta)
- distribution of the villi on the foetal chorion is localized in multiple circumscribed areas the cotyledons. In the place of cotyledons the uterine epithelium is destroyed and the
chorionic villi penetrate superficially to the connective tissue of the mucosa. By this way one
layer of the placental barrier becomes extinct.
- the epithelium of the chorionic villi differentiates and acquires the phagocytic and secretory
capability. It gives rise to a unique population of giant binoculate hormone-producing cells,
which fuse with the endometrial epithelial cells and destroy them. The areas of placentation
are limited to caruncles and the cotyledon complete with the caruncle forms placentom.
Characteristic of cow, ewe, and goat. (Fig. 8.4)
c) endotheliochorial placenta (placenta endotheliochorialis)
- decidual type of the placenta
- the chorionic villi leak into the endometrium to the vicinity of blood vessels endothelium. In
the chorion frondosum, the trophoblast gives rise to two different populations of cells: basally
located cytotrophoblast cells and superficially located syncytiotrophoblast cells, which are
formed by fusion of many trophoblast cells. The syncytiotrophoblast is highly invasive and
51
destroys both apposing endometrial epithelium and underlying connective tissue. Because of
the epithelium and connective tissue of uterine mucosa are disturbed, the placental barrier
consists only of 4 layers. This connection is considerably fixed and the uterine mucosa with
trophoblast separates after the birth like the decidua. Characteristic of the bitch and other
carnivores.
d) haemochorial placenta (placenta haemochorialis)
- a type of placenta in which all maternal layers are lost. The trophoblast differentiates into an
inner cytotrophoblast and an outer syncytiotrophoblast, which is highly invasive. The
chorionic villi penetrate into the uterine blood vessels and are washed with mother blood. This
decidual placenta consists of three layers. Occurs in humans, the most primates, insectivores,
some rodents, bat and hedgehog (placenta discoidea according to the chorionic villi
arrangement).
e) haemoendotheliochorial placenta (placenta haemoendotheliochorialis)
- the most sophisticated type of placenta, where the chorionic villi also penetrate into the
mother blood vessels, but moreover, the epithelium and mesenchyme of the chorionic villi
disappear and their naked blood vessels are directly washed by the mother blood. Only one
layer, the endothelium of foetal blood vessels, forms the placental barrier, but the foetal blood
never mixes with the blood of mother. Characteristic for rabbit and guinea pig.
52
Figure 8.1 The placental barrier. A – the epitheliochorial placenta of the saw (6 layers),
B – the syndesmochorial placenta of the cow (5 layers), C – the endotheliochorial placenta of
the dog (4 layers), D – haemochorial placenta of the mouse (3 layers), E haemoendotheliochorial placenta of the guinea pig (1 layer). The placental barrier is indicated
by the double arrow.
1,2,3 – barriers of pars foetalis, 1 – endothelium, 2 – mesenchyme, 3 – chorionic epithelium,
4,5,6 – barriers of pars materna, 4 – uterine epithelium, 5 – lamina propria mucosae, 6 endothelium
53
2
3
1
4
5
6
3
7
Figure 8.2 The diffuse placenta in the saw. 1 – chorioallantois, 2 – chorion, 3 –
endometrium, 4 – amnion, 5 – allantois, 6 – chorioallantoic villi, 7 – myometrium
2
1
3
4
5
6
7
8
9
Figure 8.3 The diffuse placenta in the mare. 1 – chorioallantois, 2 – endometrium, 3 –
amnion, 4 – allantois, 5 – yolk sac, 6 – chorioallantoic microcotyledons, 7 – endometrial cups
8 – endometrium, 9 – myometrium
54
2
1
4
3
5
6
7
Figure 8.4 The cotyledonary placenta of the ruminants. 1 – amnion, 2 – chorion, 3 –
allantois, 4 – endometrium, 5 – cotyledons, 6 – caruncle with crypts, 7 – myometrium
3
1
2
4
5
6
Figure 8.5 The zonary placenta of the bitch. 1 – chorioallantois, 2 – amnion, 3 –
endometrium, 4 – allantois, 5 – yolk sac, 6 – chorioallantoic villi
55
Figure 8.6 The discoid primate placenta. 1 – amnion, 2 – smooth chorion, 3 – villous
chorion, 4 – intervillous spaces with maternal blood, 5 – uterine cavity, 6 – endometrium, 7 myometrium
56
9 EMBRYO SHAPE DEVELOPMENT
Right after the embryo implants into the uterine wall, its cells separate into three
layers: the ectoderm, mesoderm and endoderm. Each layer will later form into different parts
of the body. In fact, the beginnings of the brain and spinal cord begin developing from the
ectoderm almost right away.
The germ disc is initially flat and round, gradually becomes elongated with broad cephalic
and narrow caudal end. The germ disc periphery is formed by the low circumvallation, the
margin of which presents the interface between embryonic and extraembryonic ectoderm.
The first suggestion of germ shape changes occur in connection with forming of axial
structures on the germinal disc ectoderm (the primitive strike and especially the neural plate),
mesoderm (segmentation of the paraxial plate, forming of the coelom) and also endoderm (the
primitive gut and the yolk sac). The significant event in the establishment of body form is
folding of the flat trilaminar embryonic disc into a somewhat cylindrical embryo. Folding
occurs in both vertical and horizontal planes and results in rapid growth of the embryo. (Fig.
9.1)
Folding of the embryo in vertical (median) plane – the embryo elongates cranio-caudally, so
that the cranial and caudal regions move ventrally and produce head and tail fold.
The head fold results from the thickening of cranial portion of the neural tube, from which the
brain primordium forms. Later, the growing head fold grows cranially beyond the
oropharyngeal membrane and overhangs the developing heart. (Fig. 9.1 C, D)
Tail fold – folding of caudal end of the embryo results primarily from the growth of the distal
part of the neural tube – the primordium of the spinal cord. As the embryo grows the tail
region projects over the cloacal membrane, the future site of anus. (Fig. 9.1 B, C)
Folding of the embryo in the horizontal plane – folding of the sides of the embryo produces
right and left lateral folds. Lateral folding results from the rapid growth of the spinal cord and
especially somites. The primordia of the ventrolateral wall underwind ventrally, forming a
roughly cylindrical embryo. (Fig. 9.1 C1, D1)
Initially, there is a wide connection between the midgut and yolk sac. However, after
cranio-caudal and lateral folding, the connection is reduced to an omphaloenteric duct and
the yolk sac cavity separates from the dorsally positioned primitive gut. (Fig. 9.1 C1, D1) The
cranial portion of the primitive gut terminates blindly (foregut) as well as on the caudal
portion (hindgut). Middle portion which is connected with the yolk sac by the
omphaloenteric duct is the midgut. (Fig. 9.1 C) The terminal part of hindgut (primordium of
descending colon) soon dilates to form the cloaca (primordium of urinary bladder and
rectum).
Concurrently, the extraembryonic ectoderm commonly with the somatopleura form amniotic
folds around the germ disc (cranial, caudal and lateral), which elevate above the surface of the
germ. (Fig. 6.2 and Fig. 6.3)
Originally wide and short umbilical stalk, due to folding of the embryo, becomes
narrower and elongates. Thereby the umbilical stalk changes to the umbilical cord (funiculus
umbilicalis). (Fig. 9.1 C, D) Its connection with the embryo shifts caudally, so that the surface
of the frontal body wall enlarges. Inside the umbilical cord the remnants of the
omphaloenteric duct and yolk sac are present. After the obliteration of the yolk sac the
umbilical cord attaches the embryo with the allantochorion.
57
Figure 9.1 Folding of embryo. A, B ,C ,D – lateral views of embryo, A1, B, C, D1 – sagittal
sections at the plane shown in A to D. Modified from Moore et al. (2013).
58
The region of attachment of the amnion to the ventral surface of the embryo is reduced to a
relatively narrow umbilical region. (Fig. 9.1 D1) As the umbilical cord develops from the
umbilical stalk, ventral fusion of the lateral folds reduces the region of communication
between the intraembryonic and extraembryonic coelomic cavities to a narrow space. After
this time the amnion forms the epithelial covering of the umbilical ford. (Fig. 9.1 D)
The somites development from the paraxial mesodermal plate is observable on the
back of embryo. Somites firstly appear in the future occipital region and soon develop
craniocaudally. They are observable like to lines of bulges, paraxial, on the primitive back.
The cranial end of the neural tube enlarges extensively (the brain primordium);
enlarged head fold underwinds below the oropharyngeal membrane and shifts the pericardial
cavity with the base of heart caudally. At this time the neural tube is widely open at the rostral
and caudal neuropores. (Fig. 9.2) The growth of heart elevates the ventral body wall, forming
the heart prominence. Somewhat later, the liver prominence elevates caudally from the
previous, conditioned by the rapid liver growth. (Fig. 9.3)
2
1
2
3
4
4
5
5
Figure 9.2 Fusion of neural folds and formation of the neural tube
1 - neural groove, 2 – rostral neuroporus, 3 – neural tube, 4 - somites, 5 – caudal neuropore
Modified from Hyttel et al. (2010).
59
somites
rostral
neuropore
caudal
neuropore
first
pharyngeal
arch
heart prominence
upper limb
bud
pharyngeal
arches
III
II
I
otic pit
lens
placode
forebrain
prominence
heart prominence
caudal prominence
Figure 9.3 Lateral view of embryo showing neural tube closing, development of somites,
primordium of lens, primordium of inner ear, development of heart and upper limb.
The frontonasal prominence (from the head fold) surrounds the ventrolateral part of
the forebrain, which gives rise to the optic vesicles that form the eyes. The frontal part of the
prominence forms the forehead; the nasal part forms the rostral boundary of the stomodeum
and nose. The stomodeum is a midline invagination of the surface ectoderm on the ventral
part of frontonasal prominence, at the point where later the mouth is formed. The stomodeum
invaginates against the foregut (primordium of pharynx, oesophagus, etc.), lying between the
brain and heart. The mesoderm between the ectoderm of the stomodeum and the endoderm of
the foregut disappears and ectoderm and endoderm appose. By this way the oropharyngeal
membrane separating the foregut from the oral primordium rises. In the same manner the
ectoderm on the caudoventral part of the embryo (tail fold) invaginates to form the
proctodeum. The proctodeum and the dilated caudal part of the hindgut, cloaca, are separated
by the cloacal membrane (future site of anus). After the perforation of both membranes the
gut obtains the communication with the amniotic cavity. (Fig. 9.4)
60
central nervous system
hindgut
foregut
proctodeum
stomodeum
developing
heart
pericardial coelom
midgut
allantois
foregut
hindgut
midgut
oro-pharyngeal
membrane
anal
membrane
septum transversum
allantois
Fig. 9.4 Cranial and caudal body folding leading to the formation of the foregut, midgut
and hindgut. Cranial and caudal ectodermal depression leading to the creation of the
oropharyngeal and anal membrane.
Before the closure of the rostral neuropore (neuroporus cranialis), on the lateral side of the
frontonasal prominence, near the hindbrain, otic placodes develop. The otic placode is a
thickening of the ectoderm from which the inner ear develops, including both the vestibular
system and the auditory system. Subsequently the otic placode invaginates into the
mesenchyme adjacent to the rhombencephalon to form the otic pit (Fig. 9.3), which then
separates from the surface ectoderm to form the otic vesicle.
At the level of the forebrain (diencephalon) the lens placodes, as a thickened portion of
ectoderm appear. (Fig. 9.3) As development proceeds, the lens placode begins to deepen and
invaginates, the opening to the surface ectoderm constricts and the lens cells form a structure
known as the lens vesicle. Consequently the lens vesicle is completely separated from the
surface ectoderm. The eyes develop as a pair of diverticula, optic vesicles, from the lateral
aspects of the diencephalon. The peripheral part of each expands to form hollow bulb of the
optic vesicles, while the proximal part remains narrow and constitutes the optic stalk.
61
The optic vesicle invaginates and is converted to the optic cup (ophthalmic cup), which
overlaps the front of the lens and reaches as far forward as the future aperture of the pupil.
The third thickening observable on the ectoderm of the frontonasal prominence, are nasal
placodes. The nasal placodes, primordia of the nasal epithelium, are bilateral oval thickenings
of the surface ectoderm, which have developed on the inferolateral parts of the frontonasal
prominence. Initially the placodes are convex, but later they are stretched and form a flat
depression. Mesenchyme around the placodes proliferates, producing horseshoe-shaped
elevations, lateral and medial nasal prominences. Depressions of nasal placodes change to
nasal pits, the primordia of the anterior nares (nostrils) and nasal cavities. (Fig. 9.5)
The nasal part of the frontonasal prominence forms the rostral boundary of the
stomodeum and nose. The paired maxillary prominences form the lateral boundaries of the
stomodeum and the paired mandibular prominences constitute the caudal boundary of the
stomodeum. The proliferation of the mesenchyme in the maxillary prominence causes them to
enlarge and grow medially towards each other and the nasal prominences. The medial nasal
prominences merge with each other to form the nasal septum, ethmoid and cribriform plate.
Moreover they form an intermaxillary segment, penetrating between maxillary prominences
and giving rise to the middle part of the lip (philtrum) and the primary palate. The lateral
nasal prominences form the alae of the nose. Each lateral nasal prominence is separated from
the maxillary prominence by a cleft called the nasolacrimal groove (later nasolacrimal duct).
(Fig. 9.5)
forehead
nasal part of
frontonasal
prominence
nasolacrimal
groove
maxillary
prominence
mandibullar
prominence
pharyngeal
arches
lens placode
nasal placode
1
2
medial and lateral
nasal prominences
3
4
Figure 9.5 Development of the face. The development of the single frontonasal prominence
and the paired maxillary and mandibular prominences. Formation of two bilateral thickenings
– the nasal and lens placode.
9.1. Development of the face
The five facial primordia appear around the large primordial stomodeum, depending on the
inductive influence of the prosencephalic and rhombencephalic organizing centres. (Fig. 9.5)
- the single frontonasal prominence
- the paired maxillary prominences
- the paired mandibular prominences
62
The paired maxillary and mandibular prominences are derivatives of the first pair of
pharyngeal arches. The growth of all prominences is based especially on the expansion of the
neural crest cell populations.
9.2. Pharyngeal pouches
Caudally, below the stomodeum, the primordial pharynx derives from the foregut.
Pharyngeal or branchial pouches form on the endodermal side between the pharyngeal
(branchial) arches and pharyngeal grooves (or clefts) form the lateral ectodermal surface of
the neck region to separate the arches. This so called pharyngeal apparatus is adequate to
branchial apparatus of a fish embryo at a comparable stage of development (branchia = gills).
In vertebrates the pharyngeal apparatus is temporary and these embryonic structures
contribute extensively to the development of organs of the head and neck region.
The endoderm of the primitive pharynx lines the internal aspects of the pharyngeal
arches and passes into the pharyngeal pouches, which develop in a craniocaudal sequence.
There are four well-defined pairs of pharyngeal pouches, the fifth pair is rudimentary or
absent. The endoderm of the pouches contacts the ectoderm of the pharyngeal grooves and
together they form the double-layered pharyngeal membranes (membranae obturantes) that
separate the pharyngeal pouches from the pharyngeal grooves.
9.3. Pharyngeal arches
Pharyngeal arches eminently contribute to the forming of the face and neck region.
Each pharyngeal arch consists of a mesenchymal core, which differentiates to a cartilaginous
rod and a muscular component after immigration of neural crest cells, contains an artery,
vein and nerve and is covered externally by ectoderm and internally by endoderm.
The first pharyngeal arch (mandibular arch) separates into two prominences, maxillary
and mandibular. The maxillary prominence gives rise to the maxilla, zygomatic bone and a
portion of the vomer. Both mandibular prominences grow together to form the mandible and
the proximal mandibular prominence also forms the squamous temporal bone.
The second pharyngeal arch (hyoid arch) contributes to the formation of the hyoid
bone.
The third and fourth pharyngeal arches form an ectodermal depression, cervical sinus
(sinus cervicalis). The second pharyngeal arch enlarges and overgrows the depression,
forming operculum. In fish the operculum forms the gill-cover. The cervical sinus
communicates with the amniotic cavity by cervical canal (canalis cervicalis). Both structures
mostly obliterate. Only sporadically the branchial cyst or branchial fistula persists.
The fifth and sixth pharyngeal arches are not discernible on the surface. The fifth arch
undergoes atrophy, while the sixth arch fuses with the fourth arch, forming a fourth-sixth arch
complex. (Fig. 9.6)
9.4. Pharyngeal grooves
Pharyngeal grooves - the head and neck regions of the vertebrates exhibit four
pharyngeal grooves (clefts) on each side, which separate the pharyngeal arches externally.
63
Only the first pair of grooves contributes to postnatal structures; persists as the external
acoustic meatus. The other grooves lie in the cervical sinus and are obliterated (see above).
Pharyngeal membranes (membranae obturantes) - form where the epithelia of the
grooves and pouches approach each other. Only the first pair of membranes contributes to the
formation of adult structures; along with the thin intervening layer of mesenchyme becomes
the tympanic membrane.
Six auricular hillocks, three mesenchymal proliferations on each side form around the first
pharyngeal groove. They derive from the first and second pharyngeal arches. The auricular
hillocks grow and join together to form the outer ear. Initially the outer ears are located in the
neck region; however, as the mandible develops, they are located on the side of the head at the
level of the eyes.
Pharyngeal
Clefts
Arches
Tongue
buds
Thyroid
diverticulum
Pharyngeal pouches
1
1
1st
2nd
2
2
3
3rd
3
4
4
4th
Ectoderm
Mesoderm
Endoderm
Esophagus
Figure 9.6 Frontal section through the pharyngeal region showing the pharyngeal
arches, clefts and pouches. Modified from Moore et al. (2013).
The body shape is given by the formation of the heart and liver prominence (see
above) on the ventral body wall. (Fig. 9.3) These prominences, based on the body growth,
subsequently relatively dwindle and the embryo becomes more straighten. As the embryo
grows the tail region projects over the cloacal membrane and elongates, forming the tail bud,
which have developed from the primitive streak. The chorda dorsalis, neural tube and caudal
portion of hindgut (tail gut) grow into the tail bud. These structures later become extinct; the
neural tube reminder is filum terminale, the chorda dorsalis is replaced by the tail vertebrae.
(Fig. 9.7)
The limb development essentially participates on the formation of the body shape. The
upper limb buds develop opposite the caudal cervical segments and the lower limb buds form
64
opposite the lumbar and upper sacral segments. The upper limb buds are visible earlier and
the lower limb buds appear 1 to 2 days later. The limb buds firstly appear as elevations of the
ventrolateral body wall. They consist of the mesenchymal core (derived from the somatic
layer of lateral mesoderm) covered by thickened band of ectoderm.
The next limb development is based on the mutual interactions of ectoderm and
mesenchyme which are regulated by the homeobox genes. The ectodermal thickening forms
an apical ectodermal ridge (AER), the rise of which is induced by the underlying
mesenchyme, known as the progress zone (PZ). Contrarily the AER induces the
multiplication of mesenchymal cells and so initiates the growth and development of the limbs
along the proximodistal axis. Some mesenchymal cells differentiate into blood vessels and
cartilage bone models.
hindgut
hindgut
mesentery
mesentery
cloaca
septum
urorectale
cloacal
membrane
ductus
allantoideus
cloacal
membrane
ductus
allantoideus
tail gut
cloaca
filum
terminale
hindgut
mesentery
urorectal
septum
urinary
bladder
phallus
urogenital
membrane
perineum
rectum
anal
membrane
ductus
allantoideus
filum
terminale
Fig. 9.7 Development of the caudal portion of the embryo. Longitudinal section showing
stages in the division of the cloaca by the urorectal septum into the anorectal canal and the
base of the urinary bladder, the urogenital sinus.
65
A
B
somites
limb
bud
axopodium
autopodium
basipodium
C
axopodium
radius
ulna
metapodium
acropodium
autopodium
apoptosis
E
D
Figure 9.8 Development of the forelimb. A – globular limb bud, B – elongation of the limb
bud. A constriction divides the limb bud to cylindrical axopodium and globular autopodium,
C, D, E – developing autopodium, which becomes paddle shaped and subdivides to
basipodium, metapodium and acropodium (future carpus, metacarpus and digits). The basic
pattern of limb development is initially the same for all domestic mammals but later becomes
modified by species-specific changes. C – carnivores, D – ruminants, pig, E – horse. The
interdigital spaces are sculptured by apoptosis. The bone morphogenetic proteins (BMP-2,
BMP-4, and BMP-7) play an important role in this process.
66
The limb buds are firstly globular, but early elongate and differentiate to the proximal
cylindrical axopodium and the distal discoid autopodium. (Fig. 9.8) The axopodium presents
the common base of a shoulder (thigh) and a forearm (shank), which by an elbow (knee) is
divided to the stylopodium (arm, thigh) and zeugopodium (forearm, shank). The autopodium
differentiates to the proximal basipodium, the middle metapodium and the distal
acropodium. (Fig. 9.8)
The distal ends of the limb buds (acropodium) flatten, to form paddle-shaped
handplates and flipper-like footplates. The mesenchymal tissue in the handplates and little
later in footplates condenses, to form digital rays. These mesenchymal condensations outline
the pattern of the fingers.
Hoxb-8, is necessary for origination of the zone of polarizing activity (ZPA). ZPA cells present the
major signalling centrum, which is responsible of craniocaudal patterning (through the production of
the retinoic acid and Sonic hedgehog (Shh) (see chapter Development of limb bones)
Firstly the digital rays of the third and fourth digits develop, later others according to animal
species. At the tip of each digital ray a part of the AER induces the development of the
mesenchyme into the mesenchymal primordia of the bones, phalanges of the digits. The areas
between the digital rays are occupied by the loose mesenchyme. This intervening mass soon
undergoes apoptosis (programmed cell death), breaks down and notches between the digital
rays are formed. (Fig. 9.7) The process of the apoptosis is probably mediated by the signalling
molecules of the transforming growth factor ß superfamily. On the ground that the intervening
regions of mesenchyme break down, individual digits separate.
The upper extremity continues outgrowth and rotates through 90 degrees so that the
elbows project posteriorly. The lower extremity rotates through almost 90 degrees medially so
that future knees face anteriorly. At this time, the cartilaginous models of the bones are
undergoing ossification from primary ossification centres within the diaphysis of each model.
From the dermomyotomes regions of the somites, myogenic precursor cells migrate into the
limb buds and later differentiate to myoblasts, precursors of muscle cells. As the long bones
form, the myoblasts aggregate to form large muscle mass, which later separates into the dorsal
extensors and ventral flexors. The motor neurons axons arising from the spinal cord enter the
limb buds and grow into the dorsal and ventral muscle masses. The sensory axons follow the
motor axons using them as the guidance.
The synovial joints appear in coincidence with functional development of the limb
muscles and their innervation.
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10 THE SKELETAL SYSTEM
The skeletal system consists primarily of bone and cartilage. It provides a supporting
framework for other body structures and protects internal organs. Cartilage is associated with
bone on articular surfaces, at interosseous connections and functions as a supporting tissue in
larynx, trachea and external ear.
Three distinct lineages generate the skeleton:
 The longitudinal plates of paraxial mesoderm become segment into paired cuboidal
blocks – the somites. Each somite differentiates into two parts. The ventromedial part
is the sclerotome - its cells give rise to axial skeleton (vertebrae, ribs and
sternum).The dorsolateral part is the dermomyotome – its cells form myoblasts
(primordium of striated muscle fibers) and those from its dermatome region form the
dermis (fibroblasts).
 The lateral plate of mesoderm generates the limb skeleton and their girdles.
 The cranial neural crest gives rise to the branchial arches, craniofacial bones and
cartilage. Some cranial bones (bones of roof and the base of scull) are mesodermal in
origin.
Mesodermal cells multiply and give rise to mesenchyme – the first, loosely organised,
embryonic connective tissue.
Mesenchyme condenses and forms membranous sheath at the place of future bone.
Chondrogenesis is rebuilding of the mesenchymal model into the cartilage model of a future
bone.
Osteogenesis or ossification is the process of remodelling of the mesenchymal or cartilage
model into the bone.
There are two major models of bone formation, intramembranous and endochondral
(endochondral) ossification. Both involve the transformation of mesenchymal cells into the
bone.
The term intramembranous ossification is used when the bones rise directly within the preexisting membranous sheath.
Endochondral ossification is a type of bone formation that occurs in pre-existing
cartilaginous models.
By both types of ossification firstly so called woven bone is formed in the process of
primary ossification. The woven bone is subsequently rebuilt into the lamellar bone by the
process of secondary ossification.
10.1. Intramembranous (desmogenous) ossification
The intramembranous ossification occurs in mesenchyme that has formed a
membranous sheet (hence the name intramembranous ossification).
Some mesenchymal stem cells (MSC) at the point named primary ossification
centrum begin to replicate and form nodular aggregations of cells usually in the vicinity of
blood vessels. The changes in morphology of MSCs occur; the cell body becomes more
round, their processes shorten and the amount of Golgi apparatus and rough endoplasmic
reticulum increases, so that the cells in aggregates become display the morphologic
characteristic of an osteoprogenitor cells. These cells begin to create an extracellular matrix
consisting of type I collagen fibrils and amorphous substance. This matrix is osteoid and the
cells that created it are osteoblasts. The osteoblasts, while lining the periphery of the nodule,
68
continue to form osteoid at its centre and some of them become incorporated within it to
become osteocytes.
Eventually, the nodular aggregations elongate. The central portions are formed by the
osteoid with osteocytes and the osteoblasts attached to the periphery produce new matter.
These formations are named bony spicules. The bony spicules subsequently become thicker
and fuse to each other, forming trabeculae, which begin to anastomose, so that the network
of trabeculae surrounds the blood vessels. As the growth continues, trabeculae become
interconnected into lamellae and woven bone is formed. The term primary spongiosa is also
used to refer to the initial trabecular network.
Later the mineralisation occurs and crystals of hydroxyapatite are deposit at collagen
fibers.
At the surface of the forming bone the surrounding mesenchyme organises into the
fibrous sheath, periosteum. The inner zone of the periosteum (cambium) attaches new layers
to the existing bone by the process of apposition.
The typical examples of the ossification directly from the mesenchyme are the flat
scull bones, some facial bones, mandible and clavicle.
10.2. Endochondral ossification
The process of the endochondral ossification begins in mesenchyme within preexisting membranous sheath. Mesenchymal models of the bones are transformed into
cartilage bone models, which later become ossified by endochondral bone formation.
Bone morphogenetic proteins (BMP-5 and BMP-7), the growth factor Gdf5, members of the
transforming growth factor ß (TGF- ß) superfamily, and other signalling molecules are
referred as endogenous regulators of chondrogenesis and skeletal development.
The most of skeleton develop by the endochondral ossification; the bones of the trunk,
limbs and some cranial bones.
Formation of the cartilage model (blastema)
In areas, where cartilage will develop, the mesenchyme condenses to form
chondrification centres. The mesenchymal cells differentiate into chondroblasts that begin to
produce the intercellular matrix of cartilage (amorphous substance and collagenous fibrils).
The cartilage model is covered by perichondrium with great amount of non-differentiated
cells of embryonic connective tissue.
Histogenesis of bone
Formation of the bone begins in a ring of perichondrium around the middle portion of
diaphysis. In the inner zone of the perichondrium (cambium), some fibroblasts differentiate
into the cells producing bony intercellular mass (osteoblasts). That way the ring of periosteal
bone forms and perichondrium within its range becomes periosteum. The term bony collar is
also used.
Within the bony collar the chondrocytes of cartilage model start to degenerate, because the
bony collar inhibits the penetration of nutrients inside. Chondrocytes lose the ability to
maintain the intercellular mass, degenerate, hypertrophy and the intercellular mass undergo
calcification. Subsequently the blood vessels penetrate through the openings formed in bony
collar by the action of osteoclasts. The osteoclasts, which differentiate in cambium, leak
deeper, destroy the partitions between hypertrophied chondrocytes and prepare the way for
the blood vessels. The blood vessels leak inside, into the spaces leaved by degenerated
chondrocytes, accompanied by the osteoprogenitor cells (osteogenic buds). (Fig. 10.1)
69
Osteoprogenitor cells of osteogenic buds proliferate and differentiate into the osteoblasts,
which begin to synthetize the bony mass on the spicules, reminders of calcified cartilage.
They use the calcified matrix as scaffolding and begin to secrete osteoid, which forms the
bone trabecules. The calcified cartilage we can distinguish in haematoxylin-eosin stained
preparations according to intensively blue colour, as deposits of bony mass are acidophilic.
Above mentioned process gives rise to primary ossification centrum inside the middle
portion of the diaphysis. Based on the widening of the bony collar the primary ossification
centrum expands longitudinally towards both epiphyses. This expansion is accompanied by
the activity of osteoclasts, which reabsorb the bone from its centrum towards epiphysis,
forming a medullary cavity.
Later the secondary ossification centres in middle portions of epiphyses develop. The
role of secondary ossification centres is analogous to the role of primary centres, with the
difference, that their growth is radial.
When the bony tissue produced by the secondary ossification centres fills up all the epiphysis,
the cartilage remains at the two places; like the articular cartilage, which stays here all the life
and epiphyseal plate or growth plate, at interface of epiphysis and diaphysis (metaphysis).
The plate is found in young ones and adolescents; in adults, who have stopped growing, the
plate is replaced by an epiphyseal line, marking the junction of the epiphysis and diaphysis.
Zones of ossification
The growing epiphyseal cartilage is continuously replaced by the newly formed bony matrix
from the diaphyseal ossification centrum.
The growth plate has a very specific morphology in having a zonal arrangement. Within the
growth plate 8 zones of ossification can be described. (Fig. 10.2)
1. Zone of resting cartilage. It is relatively inactive reserve zone at the epiphyseal end.
This zone contains normal, resting hyaline cartilage. A small, randomly oriented
chondrocytes in isogenic groups are present.
2. Zone of proliferation. In this zone, chondrocytes undergo rapid mitosis and organize
into distinct columns.
3. Zone of hypertrophy. The chondrocytes stay in columns and provide the intense
matrix production (type II collagen and proteoglycans). Consequently they undergo
hypertrophy, gradual cellular enlargement is observable.
4. Zone of calcification. The enlarged cells begin to degenerate, lose the ability to
sustain the matrix and the intercellular mass becomes calcified. Later the chondrocytes
die, leaving cavities that will later become invaded by bone-forming cells. *
5. Osteoid zone. Osteoprogenitor cells invade the area leaved by chondrocytes and
differentiate into osteoblasts, which elaborate the bony matrix. This first product is not
calcified so that the term osteoid is used.
6. Zone of ossification. The bony matrix becomes calcified on the surface of calcified
cartilage spicule. The primary trabecules of woven bone are formed.
7. Zone of resorption. Osteoclasts absorb the oldest ends of the bone trabecules,
forming the diaphyseal marrow cavity.
*Line of erosion. It is the interface between the 4th and 5th zone. The line of erosion is the
level up to blood vessels accompanied by osteoclasts and osteoprogenitor cells reach. The
osteoprogenitor cells differentiate to osteoblasts which begin to deposit the bony mass on the
calcified cartilage remnants (spicules), forming directional trabecules, which display the
direction of the ossification process.
70
A
B
C
2
3
1
4
5
D
E
6
7
10
9
8
11
Figure 10.1 Formation of a long bone on a model made by cartilage.
1 – hyaline cartilage, 2 – bone collar, 3 – hypertrophy of chondrocytes and calcification of
intercellular matrix, 4 – blood vessels penetrate the bone collar, 5 – primary ossification
centre, 6 – secondary ossification centre, 7 – epiphyseal or epiphyso-diaphysal plate, 8 –
osteoclasts, 9 – osteoblasts, 10 – osteoid, 11 – ossified bone
71
zone of resting cartilage
zone of proliferation
line of
erosion
zone of hypertophy and calcification
osteoid zone
zone of ossification
zone of resorption
Figure 10.2 Endochondral (intracartilaginous) ossification in a developing long bone
Within the range of epiphyseal plate the processes of growth and destruction are in balance,
so that the plate has constant thickness. The proliferation of chondrocytes ceases at the end of
the growth period of the organism, the epiphyseal plate is replaced by the bony mass and the
growth terminates.
The result of the primary ossification is the woven bone. The diaphysis consists of the thick
cylinder of periosteal bone (primary compacta), which ensures the growth in width, and
inside, there is the medullary cavity with red bone marrow and sporadic bony trabecules. The
epiphysis consists of woven cancellous bone trabecules.
By the secondary ossification, the primary compacta is rebuilt into the lamellar bone. The
process of transformation begins in the middle portion of diaphysis and extends towards both
epiphyses. By the enzymatic action of osteoclasts (osteolysis) numerous cavities with blood
72
vessels and osteoprogenitor cells are created within the primary compacta. The
osteoprogenitor cells differentiate to osteoblasts and newly produced mass is organised into
the lamellae of the Haversian systems. Inside the epiphysis the primary woven bone is
replaced by the lamellar spongy bone.
The bones present very dynamic system, where the remodelling processes doesn´t finish when
secondary ossification terminates, however continue for nearly all the life. Old Haversian
systems are destroyed and incurred cavities are filled with new Haversian systems. Some rests
of an old Haversian systems persist as interstitial lamellae.
10.3. Development of the bone joints
In term of phylogenesis the older type of bone connection is synarthrosis and the younger
type is diarthrosis.
The bone joints are classified according to the type of material holding the bones together to
fibrous (syndesmosis), cartilaginous (synchondrosis), osseous (synostosis) and synovial
joints. The first three types are classified as synarthrosis, the last type is diarthrosis.
During the development of fibrous joints the loose mesenchyme (interzonal
mesenchyme) between developing bones condenses and differentiates into dense irregular
connective tissue. The examples are cranial sutures or gomphosis (alveolar ligaments of
tooth).
During the development of cartilaginous joints the interzonal mesenchyme
differentiates into the hyaline cartilage, like in costochondral joints or fibrocartilage (pubic
symphysis, disci intervertebrales*).
Some synchondroses ossify during postnatal development coming to osseous joints.
The example is os coxae, developing by the growth together of os ilium, os ischium and os
pubis, or os sacrum (coalesce of five sacral vertebrae).
During the development of synovial joints (diarthrosis) the interzonal mesenchyme
between developing bones condenses only laterally, forming the capsule and ligaments and
centrally disappears. This central space develops to the synovial (joint) cavity. The rest of
loose mesenchyme adjacent to the inner side of condensed periphery gives rise to the synovial
membrane, a part of the joint capsule, secreting the synovial fluid. (Fig. 10.3)
* Discus intervertebralis consists of peripheral anulus fibrosus which surrounds the
central nucleus pulposus. Intervertebral discs join the vertebrae with the exception of atlasaxis joint.
The anulus fibrosus consists of several layers of fibrocartilage with strong bundles of collagen
fibers. The nucleus pulposus contains loose fibers suspended in a mucoprotein gel. This
jellylike tissue is the reminder of the chorda dorsalis.
73
1
A
2
3
4
8
7
5
6
9
10
11
B
C
D
Figure 10.3 Development of joints.
A – primordial joint, 1 - loose mesenchyme, 2 – condensed mesenchyme, 3 – interzonal
mesenchyme, 4 – cartilage model of a bone
B – fibrous joint, C – cartilaginous joint, D – synovial joint (diarthrosis), 5 – fibrous tissue, 6
– fibrocartilage, 7 – joint cavity, 8 – joint capsule, 9 – synovial membrane, 10 – articular
cartilage, 11 - bone
74
10.4. Axial skeleton development
The axial skeleton consists of the cranium, vertebrae, ribs and sternum.
10.4.1. The development of vertebral column
The foregoing structure of the spine in phylogenetic development is a chorda dorsalis.
The vertebrae develop from the paraxial mesodermal plates, which segment into the
somites. The ventromedial portions of paired somites, sclerotomes, give rise to the mass of
mesenchymal cells, which surround the neural tube (the primordium of the spinal cord) and
the notochord.
Each condensation of mesenchymal cells pertaining to one pair of sclerotomes consists
of loosely arranged cells cranially and densely packed cells caudally. The body of each
vertebra develops by fusion of the caudal part of one sclerotome with cranial portion of the
foregoing sclerotome. Some densely packed cells move cranially, opposite the centre of the
myotome, where they form the intervertebral disc. While the notochord regresses entirely in
the region of the vertebral bodies, it persists in the region of the intervertebral discs, thus
forming the nucleus pulposus. Laterally, the circular fibers form the anulus fibrosus. (Fig.
10.4)
CAUDALLY
nucleus pulposus
anulus fibrosus
intervertebral disc
myotome
ectoderm
somites
densely
arranged
mesenchyme
sclerotome
loosely
arranged
mesenchyme
myocoele
intersegmental nerve
arteries
notochord
CRANIALLY
body of
vertebra
Figure 10.4 Development of the vertebral column. Diagrammatic scheme illustrates that
the vertebral body forms from the caudal and cranial halves of two successive sclerotomic
masses. The intersegmental arteries now cross the vertebral bodies and the spinal nerves lie
between the vertebrae. The notochord degenerates within the vertebral body. Between the
vertebrae, the notochord expands to form gelatinous centre of the intervertebral disc – the
nucleus pulposus.
75
The two processes develop from the sides of vertebral body and turn dorsally – neural
processes (processus neurales), surround the primordium of the neural tube and fuse,
forming membrana reuniens. By this way the vertebral (neural) arches (arcus vertebrae)
are created, while the cells passing ventrolaterally from the vertebral body develop into the
costal processes and ribs. Later from the vertebral arch the process, spiny process (processus
spinosus) grows dorsally.
Firstly chondrification centres appear in each mesenchymal vertebra. The two centres
of vertebral body fuse at the end of embryonic period to form cartilaginous centrum and
concomitantly the two centres in the neural arches fuse to each other and with the
cartilaginous centrum. The chondrification spreads until the cartilaginous vertebral column is
formed.
Subsequently the two primary ossification centres form in the future vertebral body
and fuse to form a single centrum. Other ossification centres develop in each half of the
vertebral arch. At birth, each vertebra consists of three bony parts connected by the cartilage.
When the vertebrae are articulated with each other, the bodies form a strong pillar for the
support of the head and trunk, and the vertebral foramina constitute a canal for the protection
of the spinal cord (medulla spinalis). In between every pair of vertebrae are two apertures, the
intervertebral foramina, one on either side, for the transmission of the spinal nerves and
vessels.
Cranial and caudal articular facets on each vertebra act to restrict the range of movement
possible. These facets are joined by a thin portion of the neural arch called the pars
interarticularis.
A
chondrification
centers
spinal
cord
notochord
B
neural arch
primary
ossification
centers
costal process
centrum
Fig. 10.5 Stages of vertebral development. A – mesenchymal vertebra. The two
chondrification centres appear in each centrum and fuse to form a cartilaginous centrum.
Concomitantly, the centres in the neural arches fuse with each other and the centrum. B –
primary ossification centres in cartilaginous vertebra.
76
10.4.2. Development of the ribs and sternum
The ribs develop from the mesenchymal costal processes of the thoracic vertebrae.
They become cartilaginous during the embryonic period and the chondrification extends from
the dorsal end ventrally. The sites of emanation of the costal processes from the vertebral
bodies are later rearranged and replaced by costovertebral synovial joints (artt.
costovertebrales). The ventral ends of ribs foundations come near, attach to one another and
fuse craniocaudally, forming the paired mesenchymal bands, sternal bars. The sternal bars
move medially and fuse craniocaudally in median plane. The chondrification continues from
the ribs to form cartilaginous models of manubrium, sternebrae and xiphoid process.
The ossification of the ribs begins from the ossification centres in their dorsal parts and
progresses ventrally. The sternum ossifies from the ossification centres inside the individual
sternebrae. The cartilage persists only within the processus xiphoideus.
10.4.3. Development of the cranium
The cranium (skull) is the cranial continuation of the axial skeleton, which develops from the
mesenchyme around the developing brain. The cranium consists of:
1) The neurocranium – the protective case for the brain
2) The splanchnocranium (viscerocranium) – the skeleton of the face protecting the
cranial parts of the digestive and respiratory system.
Evolutionary, during the phylogenetic development, the cranial and caudal portion of the skull
are referred. The cranial portion of the skull is older, so called paleocranium. It includes
nasal, orbital and auditory compartments up to the output of the VIIth brain nerve. The caudal
portion, so-called neocranium associates with the cranial one later. The caudal part develops
from the segmented mesoderm and it is the rest of skull as far as the occipital foramen
(foramen magnum).
During the ontogenetic development of the skull, three developmental levels may be
described: the desmocranium, the chondrocranium and the osteocranium.
The desmocranium develops from the mass of non-segmented mesoderm at the
cranial end of the notochord in the early embryo (head plate). The head plate gives rise to the
mass of mesenchyme, which surrounds the developing primitive brain, condenses and forms
the mesenchymal capsule. The mesenchyme closes the brain dorsally, orally and laterally and
overgrows the eye and auditory pouches. The caudal part of the mesenchymal capsule
develops from the occipital sclerotomes and temporarily appears segmentation.
The chondrocranium develops from the part of the mesenchymal ground, but the
chondrification does not occur within all the ground. The first sign of the chondrification is
the appearance of two pairs of cartilage plates around the cranial end of chorda dorsalis. The
caudal pair is parachordalia and the cranial pair trabeculae. By the fusion of cartilages the
cartilaginous basal plate rises. Within the basal plate the cranial non-segmented prechordal
part and the caudal segmented chordal part is possible to distinguish. From the prechordal
part the temporal, orbital and ethmoid areas develop, the chordal part is the base of occipital
and auditory compartment. The components of the basal plate are also hypophyseal cartilages
around the developing pituitary gland and cartilaginous envelops of the olfactory, auditory
and balance apparatus. (Fig. 10.7)
The osteocranium develops both by the endochondral (from the cartilage) and
membranous (from the mesenchyme) ossification. For example the calvaria develop by direct
membranous ossification without a cartilaginous precursor. The bones of the skull base
develop through the cartilage model of the future bone.
77
The development of the skull continues with ossification centres arising within the
mesenchyme (membranous ossification) adjacent to the developing brain to form the flat
bones of the calvar vault, the paired frontal and parietal bones. In contrast, the primordial
elements of the chondrocranium begin to undergo endochondral ossification to form the
bones of the basicranium (sphenoid, petrous part of temporal and occipital bones) and the
nasal ethmoid significantly later in foetal life. (Fig. 10.6) The ossification pattern of these
bones has a definite sequence, beginning with the occipital bone, body of sphenoid,
presphenoid, and the ethmoid bone. The sphenoethmoidal and sphenooccipital synchondroses
and the septal cartilage persist to allow the forward growth of the cranial base.
endochondral ossification
intramembranous ossification
5
3
4
H
2
A
C
B
E
D
F
11
6
1
I
G
J
7
8
K
L
10
12
9
M
13
Figure 10.6 Schema of a foetal cranium showing bones which develop directly from the
mesenchyme (intramembranous ossification) and bones which develop through preexisting cartilaginous model (endochondral ossification). Modified from Horký et al.
(1984).
1 – os incisivum, 2 – os nasale, 3 – os frontale, 4 – os parietale, 5 – os interparietale, 6
– os lacrimale, 7 –vomer, 8 – os palatinum, 9 – os zygomaticum, 10 – os pterygoideum, 11 –
squama ossis occipitalis, 12 – maxilla, 13 – mandibula
A – concha nasalis dorsalis, B – concha nasalis ventralis, C – conchae olfactoriae, D –
lamina perpendicularis ossis ethmoidalis, E – ala orbitalis ossis presphenoidalis, F – ala
temporalis ossis sphenoidalis, G – os petrosum, H – os occipitale, I – pars lateralis ossis
occipitalis, J – corpus ossis presphenoidalis, K – corpus ossis sphenoidalis, L – corpus ossis
occipitalis, M – os hyoideum
78
1
2
8
3
4
5
6
7
9
Figure 10.7 The development of the cartilaginous neurocranium (chondrocranium).
Individual cartilages fuse forming the cartilaginous base of the developing cranium. Later,
endochondral ossification of the chondrocranium forms the bones in the base of the cranium.
1 – nasal capsule, 2 – base of eye, 3 – base of sphenoid bone, 4 – otic vesicle, 5 – parachordal
cartilages, 6 – occipital somites, 7 – neck somites, 8 – hypophysis cerebri, 9 - notochord.
Modified from Horký et al. (1984).
Neurocranium
The bones of the neurocranium, which develop by the membranous ossification, are:
os parietale, os occipitale, os frontale, os lacrimale, os nasale, vomer, squama ossis
temporalis. Os parietale and os occipitale develop from the paraxial mesoderm of the occipital
sclerotomes, others from the non-segmented mesoderm of the head plate.
The bones of the neurocranium, which develop by the endochondral ossification, are:
os ethmoidale, corpus, alae minores et majores ossis sphenoidalis, basis ossis occipitalis, pars
petrosa ossis temporalis. The two lastly named bones develop from segmented paraxial
mesoderm, others from the head plate.
Splanchnocranium
The ground of splanchnocranium attaches to the ventral part of the neurocranium. The
bones of the splanchnocranium develop from the first two pharyngeal arches. The most of its
mesenchyme is derived from the neural crest. Neural crest cells migrate into the pharyngeal
arches and form the connective tissue and bones of craniofacial structures. The Homeobox
(Hox) genes regulate the migration and the subsequent differentiation of the neural crest cells
and are crucial for the patterning of the head and face.
79
Cartilaginous splanchnocranium
 The first pair of the pharyngeal arches transversally separates into two prominences;
the dorsal – maxillary and the ventral – mandibular prominence. Inside the dorsal
ends of mandibular prominences the cartilage plates form (Meckel cartilages). The
dorsal ends of Meckel cartilages reach the skull base and form two inner ear bones, the
malleus and incus. The ventral ends of the mandibular prominences, cranioventrally
oriented, fuse together, forming the mandible. Later the mandible undergoes
intramembranous ossification.
 Inside the mesenchyme of the dorsal ends of the second pharyngeal arches similar
cartilage plates form (Reichert cartilages), parallel with previous. The Reichert
cartilages form the stapes of the middle ear and the styloid process of the temporal
bone. The ventral ends give rise to stylohyoid and ceratohyoid, the lesser horns and
the superior part of the hyoid bone, by the intramembranous ossification.
 The third arch cartilages give rise to the greater horns and the inferior part of the body
of the hyoid bone.
 The fourth pharyngeal arch cartilages fuse to form cartilago thyroidea and other
laryngeal cartilages, except for the epiglottis.
Membranous splanchnocranium
Intramembranous ossification occurs in the ventral parts of maxillary and mandibular
prominences of the first pharyngeal arch. From the maxillary prominence os maxillare, os
zygomaticum and squama ossis temporalis develop. The squama ossis temporalis becomes
part of the neurocranium. From the mandibular prominence the mandible develops.
10.5. Development of limb bones
The appearance of individual animal species limbs is given by the living conditions
and environment. During the phylogeny from the underdeveloped limbs of the amphibians the
perfect limbs of mammals developed. In birds the upper limb changed into the wing. In some
mammals due to necessity of quick movement the number of fingers is reduced, autopodium
becomes straighten and only the fingers near the axis of the leg stay in contact with the earth.
Other fingers undergo regression. (Fig. 9.8) In other animals, which move slower (carnivores)
the thumb is reduced or in flat-foot individuals (man, primates and bear) no fingers undergo
regression.
The limb bones develop from mesenchymal blastema by the condensation of
mesenchyme in the limb buds. The mesenchymal bone models then undergo chondrification
to form hyaline cartilage bone models. The number of cartilage centres responses to the
number of future bones. The models of upper limbs bones appear slightly before those of the
lower limbs. The bone models appear in a proximodistal sequence. The patterning in the
developing limbs is regulated by homeobox-containing (Hox) genes.
The development of the forelimb is in relation to the last four neck and the first thoracic
somites. The hindlimb develops in relation to last four lumbal and first three sacral somites.
Ossification then replaces the existing cartilage except in the regions of articulation, where
cartilage remains on the surface of the bone within the joint.
The distal ends of the limb buds (acropodium) flatten, to form paddle-shaped
handplates and flipper-like footplates. The mesenchymal tissue in the handplates and little
later in footplates condenses, to form digital rays. These mesenchymal condensations outline
the pattern of the fingers. Firstly the digital rays of the third and fourth digits develop, later
others according to animal species. At the tip of each digital ray a part of the AER (the
ectodermal thickening forms an apical ectodermal ridge) induces the development of the
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mesenchyme into the mesenchymal primordia of the bones, phalanges of the digits. The areas
between the digital rays are occupied by the loose mesenchyme. This intervening mass soon
undergoes apoptosis (programmed cell death), breaks down and notches between the digital
rays are formed. The process of the apoptosis is probably mediated by the signalling
molecules of the transforming growth factor ß superfamily. On the ground of the intervening
regions of mesenchyme break down, the individual digits separate.
Limb bud formation begins with the activation of mesenchymal cells in the lateral somatic mesoderm
by the signals from the axial structures. These signals lead to the expression of fibroblast growth
factor-10 (Fgf-10), retinoic acid and T-Box factors (Tbx-4 and Tbx-5) in the prelimb mesoderm. Fgf10 specifies the position of limb buds and formation of ectodermal thickening, the apical ectodermal
ridge (AER), which plays a primary role in the organisation of the limb in proximodistal axis. Tbx-4
and Tbx-5 specify whether a forelimb or a hind limb develop. Experimental removal of AER results in
truncation of limb. Fgf-10 also stimulates the overlying ectoderm to produce Fgf-8, which stimulates
the underlying mesenchyme to produce Hoxb-8, which is necessary for origination of the zone of
polarizing activity (ZPA). ZPA cells present the major signalling centrum, which is responsible of
craniocaudal patterning (through the production of the retinoic acid and Sonic hedgehog (Shh)
protein .As the limb elongates, the proximal part (autopodium) appears cylindrical and the distal part
(acropodium) becomes paddle-shaped. Simultaneously, the limb bud bends ventrally; ventral surface
becomes the medial surface. Subsequently, the limbs rotate approximately 90º along the proximodistal
axis, so that cranial margins of paddle-shaped acropodia move medially.
Finally, the dorsoventral patterning is ensured by WNT signalling factors.
10.6. Development of avian skeleton
Similarly like in mammals the axial skeleton develops from the mesenchymal
blastema originating from the ventromedial portions of paired somites, sclerotomes. The
ossification of vertebrae appears craniocaudal sequence. One sclerotome, due to the fusion of
the caudal and cranial portion of neighbouring vertebrae, belongs to two consecutive
vertebrae.
The avian skull consists of the neurocranium and splanchnocranium. The bones of the
neurocranium develop either intramembranous or endochondral ossification. The bones of
splanchnocranium develop from the first three pharyngeal arches.
In the domestic fowl usually 8 pairs of ribs develop from the processus costales of
thoracic vertebrae, but the caudal pair during the development disappears. The sternum
creates by the fusion of costal ventral ends and undergoes endochondral ossification from
ossification centres inside individual sternebrae.
The bones of wings (modified upper limb) develop by the endochondral ossification
with the exception of scapula and os coracoideum.
The three elements of pelvic girdle, os ilium, os ischium and os pubis, develop from
single mesenchymal condensation. Commonly with synsacrum, developing by the fusion of
caudal thoracic, lumbar, sacral and some caudal vertebrae, they form the pelvis. Symphysis
ossis pubis does not develop and the pelvis stays widely opened ventrally.
The hindlimb development – the girdle condensation is completely continuous with
the compact, cylindrical femoral condensation at the region of the future acetabulum.
The limb skeleton is formed from a condensation which has the shape of letter Y. The distal
arms of the Y will give rise to the tibia and fibula, the main stem to the femur. Early
chondrogenic centres form in all three bases of the pelvis and in the diaphyseal regions of the
femur, tibia and fibula. The chondrified models of the bones are separated by the zones of
densely packed mesenchyme at sites of future joints. The subsequent ossification of
chondrified bone models has the proximo-distal sequence.
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11 MUSCULAR SYSTEM
11.1. Smooth muscle development
Smooth muscles develop from the splanchnopleure of the lateral mesodermal plate by
the differentiation of mesenchymal cells. Mesenchymal cells pull in their processes, elongate
and become spindle-shaped. The contractile structures - myofilaments start to differentiate
within the cytoplasm.
Smooth muscle develop in different portions of the body; it is found especially within the
walls of blood vessels (such smooth muscle specifically being termed vascular smooth
muscle), large lymphatic vessels and in the wall of organs (the urinary bladder, male and
female reproductive tracts, gastrointestinal tract, respiratory tract). Moreover it forms musculi
arrectores pilorum of the skin, the ciliary muscle and the iris of the eye.
Heart muscle development is taken in chapter „The development of heart“ (see chapter 12).
11.2. Striated muscle development
Striated muscle develops mainly from the segmented mesoderm of somites, its
myotomes. Only some head muscles originate from the non-segmented mesoderm of head
plate.
The myotomes positioned dorsolaterally from the neural tube, initially keep their metameric
arrangement (after the separation of sclerotome, the reminder of somite - dermomyotome
delaminates to ventral myotome and dorsal dermatome).
The cells of myotomes, myogenic mesenchymal cells, in the process of myogenesis pass
through several mitotic divisions before becoming post-mitotic myoblasts. Proliferation of
myogenic cells is caused through the action of growth factors, such as FGFs and transforming
growth factor-ß. Post-mitotic myoblasts are elongated spindle-shaped cells, which begin to
synthetize contractile proteins actin and myosin.
The mass of myoblasts grows into the future body wall, between the ectoderm and
somatopleura. This mass of myoblasts respective to one myotome is named myomere.
Myomeres are separated with transversally oriented mesenchymal partitions - myosepta.
Such original segmentation (metameric arrangement) is kept in lower vertebrates; in higher
vertebrates the original segmentation is covered.
The myoblasts originating from one myotome later fuse to form elongated, multinucleated,
cylindrical structures – myotubes. The fusion of myoblasts involves the alignment into the
chains, adhesion and final fusion, which appears to be mediated by a set of metalloproteinases
called meltrins.
During or after the fusion of myoblasts, myofibrils and myofilaments develop in the
cytoplasm of the myotubes. Transversal striation appears relatively early. Nuclei of original
myoblasts are pushed towards the periphery and finally they are located below the
sarcolemma. After this event, long and narrow myotubes are named muscle fibers (following
the development by the fusion of original cells, myoblasts, the muscle fibre can be named
syncytium).
As the myotubes develop, they become invested with external laminae, which
segregate them. Fibroblasts produce the perimysium and epimysium layers and the
endomysium is the product of muscle fibers (lamina fibroreticularis). Some individual
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myoblasts, called satellite cells, take up position between the sarcolemma of the muscle fibre
and the basal lamina in which each muscle fibre encases itself. After muscle damage, the
satellite cells can proliferate and fuse to regenerate muscle fibres.
Muscle fibers increase in the size and diameter during the first year after the birth, later their
ultimate size depends on the amount of exercise.
somite
dermatome
myotube
myotome
sclerotome
myoblasts
myofibrils
adhesion of
myoblasts
muscle fibre
- syncytium
Figure 11.1 Stages of a skeletal muscle fibre development. Mesenchymal cells of
myotomes undergo several mitotic divisions before becoming postmitotic myoblasts. The
second step is an alignment of the myoblasts into chains and the third step is the cell fusion
with ultimate union of their plasma membranes.
Each myomere has its epaxial (dorsal) and hypaxial (ventral) part. Epaxial portions obtain
their innervation from the dorsal branches of spinal nerves and the hypaxial portions from the
ventral branches of spinal nerves. Some ventral portions of myomeres give rise to limb
muscles; therefore the limbs are innervated from the ventral branches of spinal nerves.
Dorsal thoracic muscles – keep their original metameric arrangement in lower vertebrates
(fish) but mostly fuse in bigger units in higher vertebrates.
83
Some deep thoracic muscles between neighbouring vertebrae (mm. intertransversarii, mm.
interspinales) are short and have original segmentation - unisegmental muscles.
M. rectus capitis, mm. rotatores origin by the fusion of two myomeres - bisegmental
muscles. By the fusion of three or four myomeres long muscles develop (m. splenius, m.
multifidus) – plurisegmental muscles.
Ventral thoracic muscles - differentiate from the ventral (hypaxial) parts of myomeres.
Some of them shift their tentacles or move fully from the place of origin. E.g. a diaphragm
developed from the ventral portions of neck myomeres.
The metamery persists in the thoracic region (mm.intercostales) and in the abdominal region
(mm. intertransversarii of spinal cord lumbal part). Plurisegmental origin in the thoracic
region have m. transversus thoracis and mm. levatores costarum, in the abdominal region
myomeres fuse in flat abdominal muscles.
Head muscles differentiate mostly from the mesenchyme of pharyngeal arches.
From the mesenchyme of the first pharyngeal arch chewing muscles, muscles of a soft palate
and muscles inside the inner ear develop. They are innervated with n. trigeminus.
The second pharyngeal arch gives rise to skin muscles and mimic muscles of face. They are
innervated with n. facialis.
From the third pharyngeal arch the pharyngeal muscles differentiate innervated with n.
glossopharyngeus.
From the fourth pharyngeal arch muscles of larynx develop.
Lingual muscles develop from the first four occipital myotomes.
Eye muscles develop from the mesenchymal blastema in the vicinity of eye.
Limbs muscles develop from the hypaxial parts of myomeres; with this innervation from
ventral spinal horns corresponds. Myoblasts, which origin from the four neck myotomes and
the first thoracic myotomes in forelimb and from the four lumbar and three sacral myotomes
in the hindlimb, move into the limbs buds. The segmentation is in limbs fully covered.
During the ontogenesis muscles of forelimb develop earlier then muscles of hindlimb.
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12 DEVELOPMENT OF THE BLOOD CELLS, VASCULAR SYSTEM AND
HEART
The circulatory system is the first functional organ system developing in the organism. It
includes the heart, arteries, veins and blood. During the second week of development
mesodermal cells in the wall of the yolk sac form blood islands (clusters of hemangioblasts)
and differentiate into peripheral angioblasts that form endothelial cells and inner cells,
primitive blood cells. These blood islands coalesce into larger units and the endothelial cells
form tubes establishing the first blood vessels. This process is referred to as vasculogenesis.
Subsequently, blood islands form also in the mesenchyme of the embryonic body and blood
vessels develop by the same manner.
The first generation of vessels forms new vessels by sprouting. This process is referred to as
angiogenesis.
Two, parallel endocardial tubes form in cardiogenic mesoderm (cardiogenic field) (Fig.
12.1) at the end of the third week of embryonic development by the coalescence of bloodforming cavities. Then, the fusion of endocardial tubes begins at the cranial end and extends
caudally. The endocardial tubes fuse with circulatory system and the heart begins to beat at 22
to 23 days of gestation. Blood flow begins during fourth week of embryonic development.
A
1
B
7
6
4
9
8
1
10
5
2
C
3
B
11
1
Figure 12.1 Formation of the cardiogenic field in the visceral mesoderm in the anterior
part of the embryo. A - Dorsal view of embryo after removal of the amniotic fold. 1 – the
cardiogenic field (anteriorly positioned horseshoe-shaped structure), 2 – neural groove, 3 –
primitive streak, 4 – primitive node, 5 – cut edge of amniochorionic fold. B – transverse
section of embryo at the line „B“. 6 – ectoderm, 7 – mesoderm, 8 – endoderm, 9 intraembryonic coelom, 10 – visceral mesoderm. C – axial longitudinal section of embryo. 11
– pericardial cavity. Modified from Hyttel et al. (2010).
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12.1. Formation of blood cells (haemopoiesis)
The blood cells formation in a prenatal and postnatal period proceeds during the
ontogenesis.
The prenatal haemopoiesis occurs in three overlapping periods: mesoblastic, hepatolienal and medullary.
The mesoblastic period
This period takes approximately the first third of embryonic development. It occurs in the
yolk sac. The first primitive blood cells, named hematogonia or megaloblasts according to
its size 15 – 20 µm, develop from the blood islands.
The hepatolienal period
This period continue the middle third of pregnancy. The haemopoiesis develops in the
mesenchymal base of the liver and the spleen. The mesenchyme provides the precursors of
granulocytes, erythrocytes and megakaryocytes. Later also lymphopoiesis develops in the
spleen.
The medullary period
This period presents the last third of pregnancy. The haemopoietic activity is located in the
bone marrow and more over in lymph nodes and spleen. That is why the period is also named
medulolymphatic period.
In the postnatal period the medulolymphatic haemopoiesis continues. Formation of
blood elements is concentrated into the red bone marrow and some lymphoreticular or
lymphatic organs.
12.2. Heart
The heart develops as a paired organ from the mesoderm of a heart or cardiogenic plate
(similarly like in lower animals). This horseshoe-shaped cardiogenic field surrounds the
cranial portion of the germ disc. (Fig. 12.2 A)
Within the heart plate small discrete spaces develop, enlarge and fuse forming the paired
pericardial cavity. In consequence of embryonic folding the pericardial cavity moves
ventrally bellow the cranial end of a foregut. The mesoderm of the heart plate between the
foregut and the pericardial cavity becomes thicker and forms epimyocardial plate.
Some cells of the epimyocardial plate differentiate to endothelial cells, which limit endothelial
pouches. Endothelial pouches later fuse forming paired horseshoe-shaped endothelial tube,
cardiogenic tube, cardiac tube, (Fig. 12.2 B, C) the base of endocardium.
Right and left pericardial cavities come near and fuse to a single pericardial cavity into
which the epimyocardial plate with cardiogenic tube inside comes down.
After the reposition of cardiogenic tube due to the craniocaudal folding of the embryo, the
anterior extensions of the horseshoe develop into the two ventral aortae, (Fig. 12.2 E) whereas
the posterior arcuated portion makes contact with the developing venous system. (Fig. 12.2 E,
F)
The lateral folding of the embryo moves the lateral sides of the germ disc ventrally and
towards each other in the midline of the embryo. This folding brings the two ventral aortae
gradually closer to each other ventral to the foregut. Finally the two ventral aortae fuse to a
single cardiac tube. (Fig. 12.2 G) The caudal portion of the dorsal aortae fuses as well. (Fig.
12.2 G)
The cardiac tube is connected with a roof of pericardial cavity by the mesocardium dorsale,
a duplicature of the pericardial wall. Later the mesocardium partially disappears, remains
within only the cranial and caudal portion of the cardiac tube.
86
A
B
3
2
1
D
C
3
3
2
2
3
E
F
3
2
6
4a
4
4
5
G
3
H
7
8
4
10
87
11
12
I
16
15
13
14
Figure 12.2 Positioning of the developing heart and development of the dorsal and
ventral aortae.
A – dorsal view of the embryo, 1 – cardiogenic field located anteriorly
B – as a result of cranio-caudal folding of the embryo the cardiogenic tube moves
caudoventrally, 2 – horseshoe-shaped cardiogenic tube, 3 – dorsal aortae
C – dorsal aortae approach the cardiogenic tube
D – the cardiogenic tube is brought to a position ventral to the dorsal aortae
E – fusion of the dorsal aortae with cardiogenic tube, anterior extensions of which give rise to
ventral aortae. The vitelline veins approach the cardiogenic tube caudally. 4 – ventral aortae, 5
– vitelline veins
F – lateral folding of the embryo brings the posterior portions of the ventral aortae medially,
closer to each other. Later posterior portions of the ventral aortae fuse, forming a single
cardiac tube. Posterior portion of the cardiac tube becomes continuous with venous system. 4
– anterior portions of the ventral aortae, 4a – posterior portions of the ventral aortae, 6 –
cranial portion of the vitelline veins
G – the caudal portions of the dorsal aortae fuse and posterior portions of the ventral aortae
fuse as well, forming cardiac tube. 7 – fused caudal portions of the dorsal aortae, 8 - fused
ventral aortae
H – the cardiac tube expands in diameter and differentiates to the bulbus cordis, ventricle and
atrium. 10 – bulbus cordis, 11 – ventricle, 12 - atrium
I – positioning of the developing heart within the pericardial cavity, below the primitive gut.
13 – pericardial cavity, 14 – septum transversum, 15 – primitive gut, 16 - forebrain
Modified from McGeady et al. (2006).
88
12.3. Segmentation of the cardiac tube and the curvature formation
The anterior cardiac tube is continuous with the two ventral aortae and the posterior end fuses
with the cranial portion of the vitelline veins. (Fig. 12.2 G).
The tube expands in diameter and begins to pump blood out into the ventral aortae, the aortic
arches, and dorsal aortae. In return it receives the venous blood by the vitelline and umbilical
veins at the posterior pole. Some portions of the cardiac tube expand more than others so that
four dilatations separated by narrower channels are observable.
The most caudal portion is sinus venosus, which is separated by the groove sulcus
terminalis from more cranial atrium. The atrium is separated by means of sulcus
atrioventricularis from the base of ventricle and the ventricle is separated by means of
sulcus bulboventricularis from the most cranial portion bulbus cordis, continuing as truncus
arteriosus .(Fig. 12.3 A)
A
B
8
6
1
7
1
0
2
5
1
4
4
5
9
9
2
3
3
C
11
D
10
10
4
1
1
2
2
4
9
9
12
3
3
Figure 12.3 The segmentation of cardiac tube and heart loops formation.
1 – truncus arteriosus, 2 - bulbus cordis, 3 – ventricle, 4 – atrium, 5 – sinus venosus, 6 –
sulcus bulboventricularis, 7 – sulcus atrioventricularis, 8 – sulcus terminalis, 9 – septum
transversum, 10 – aortic arches, 11 – dorsal aortae, 12 – auricles. Modified from McGeady et
al. (2006).
89
Because the cardiac tube outgrows the pericardial cavity and because the tube is fixed by the
mesocardium at both ends, the tube becomes U-shaped with the loop at level of ventricle
(bulbo-ventricular loop). In this manner cranial portion of the cardiac tube shifts caudally,
ventrally and to the right. The top of this curvature is adequate to the future apex cordis. The
curvature divides the cranial portion of cardiac tube to descending segment following atrium
and ascending segment continuing as bulbus cordis. (Fig. 12.3 B, C, D) The descending
segment is adequate to the left ventricle and the ascending segment to the right ventricle.
This curvature forms the heart bulge which is clearly visible at the outside of the embryo
during the third week of gestation (in cattle around Day 22 of gestation).
Subsequently the loop at level of the atrium forms (atrial loop). The atrium commonly with
sinus venosus (caudal portion of cardiac tube ) shifts cranially, dorsally and to the left. The
cardiac tube becomes S-shaped instead of a U (in cattle around Day 23 of gestation).
The foundation of the atrium evaginates on the left and right side forming the heart auricles
(angular or ear-shaped processes) attached to the sides of bulbus cordis (Fig. 12.3 D)
12.4. Septation of the heart and formation of the heart chambers
During the next development the heart becomes divided by the complex of septa to the right
and left compartment.
This process includes the following steps:






Incorporation of the sinus venosus into the atrium
Septation of the atrioventricular canal - septum intermedium
Development of the atrial septum
Formation of the ventricular septum
Septation of the cono-truncus
Development of aortic and pulmonary valves
12.4.1. Incorporation of the sinus venosus into the atrium
Firstly the omphalomesenteric or vitelline veins open into the sinus venosus followed
shortly by the umbilical and cardinal veins. The connection of these three pairs of veins is
symmetrical and by this way the right and left sinus horns are formed. (Fig. 12.4 A)
Gradually, the opening from the sinus venosus into the atrium shifts to the right and
the right sinus horn merges into the atrium (Fig. 12.4 B) The lateral border line between the
incorporated sinus and the right atrium forms the crista terminalis whereas the medial one
develops to the septum secundum (see „Development of the atrial septum“ later in this
chapter).
The anterior portion of the right sinus horn develops to cranial vena cava that opens to the
right atrium and the posterior one develops to the corresponding part of the caudal vena
cava. The left sinus horn develops into the coronary sinus. (Fig. 12.4 C) While the sinus
venosus is incorporated into the right side of the atrium, the pulmonary veins start to open
into the left side of the atrium. Firstly there is only single opening from the common cavity
into which four pulmonary veins drain. Later, however, the common cavity is incorporated
into the atrium resulting in four individual openings for the pulmonary veins.
90
Figure 12.4 Incorporation of the sinus venosus into the atrium. Development of the
cranial and caudal vena cava. Modified from Sadler (2006)
91
12.4.2. Septation of the atrioventricular canal - septum intermedium
In the fourth week, the left, right, superior and inferior endocardial cushions appear inside
the atrioventricular canal. The superior and inferior endocardial cushions fuse to form the
septum intermedium, creating left and right atrioventricular canals. (Fig. 12.5) The left
and right endocardial cushions give rise to the atrioventricular valves.
3
2
6
1
2
5
1
7
8
4
9
Figure 12.5 Septation of the common atrioventricular canal. Arrows indicate direction of
growth. 1 – superior and inferior endocardial cushions, 2 – atrioventricular canal, 3 – atrium,
4 – ventricle, 5 – bulbus cordis, 6 – truncus arteriosus, 7 – septum intermedium, 8 – right
atrioventricular canal, 9 – left atrioventricular canal. Modified from McGeady et al. (2006).
12.4.3. Development of the atrial septum
The membranous septum primum grows down from the caudodorsal roof of the primitive
atrium towards the septum intermedium. This crescent-shaped fold separates right and left
atrium which stay connected only through a small opening ostium primum. Later septum
primum fuses ventrally with septum intermedium but before this closure programmed cell
death in the dorsal region of septum results in formation of ostium secundum. It allows the
continued blood flow from developing the right atrium to the left one.
The septum secundum begins to develop in the fifth week of gestation. It is a thick muscular
septum which grows from the craniodorsal roof of the primitive atrium, to the right of the
septum primum, and extends towards the septum intermedium. The septum secundum grows
until it has completely covered the ostium secundum, but retains an oval opening, the
foramen ovale. The dorsal portion of the septum secundum fuses with the septum primum
whereas the ventral portion establishes a valve regulating the blood flow from the primitive
right atrium to the left atrium. (Fig. 12.6)
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1
10
A
1
B
11
2
3
9
3
4
8
5
12
6
7
16
C
D
13
13
1
14
14
1
11
15
15
13
13
E
F
1
16
17
19
17
18
Figure 12.6 Partitioning of the heart leading to the formation of left and right atria and left and
right ventricles. 1 – septum primum, 2 – common atrium, 3 – septum intermedium, 4 – left
atrioventricular canal, 5 – common ventricle, 6 – primordium of interventricular septum, 7 –
interventricular sulcus, 8 – right atrioventricular canal, 9 – caudal vena cava, 10 – cranial vena cava,
11 – ostium primum, 12 – elongation of interventricular septum, 13 – ostium secundum, 14 – left
ventricle, 15 – right ventricle, 16 – septum secundum, 17 – foramen ovale, 18 – cavitations in
myocardium, 19 – direction of blood flow through foramen ovale. Modified from McGeady et al.
(2006).
93
12.4.4. Formation of the ventricular septum
During the heart tube curvation the junction between bulbus cordis and ventricle shifts
ventrally. The narrower portion of the bulbus cordis, conus cordis is the continuation of
truncus arteriosus. The lower portion of the bulbus cordis adjacent from the right to ventricle
is dilated and the transition between the bulbus cordis and ventricle is marked externally by a
groove and internally by a muscular fold that develops to the muscular part of the
interventricular septum. (Fig. 12.6) The interventricular septum grows from the bulboventricular groove dorsally towards the septum intermedium. The ventricles firstly are not
separated completely; an interventricular foramen persists for some time. Gradually this
opening is closed by the membranous part of the ventricular septum, which develops from the
inferior endocardial cushion.
12.4.5. Septation of the cono-truncus
To complete the division of the cardiac tube into the right and left part, the bulbus cordis and
the truncus arteriosus also need to be divided to two channels.
Two longitudinal conotruncal septa appear on opposite walls of the cono-truncus,
developing spirally both proximally and distally, eventually fusing to split the outflow tract
into the ascending aorta and pulmonary trunk. (Fig. 12.7)
Inferiorly, the conotruncal septa also fuse with the superior endocardial cushion, forming the
membranous ventricular septum, and finally fuse with the muscular ventricular septum,
completing the division of the ventricles. The aorta gets connected to the left ventricle and a.
pulmonalis to the right ventricle.
A
B
developiong aortico-pulmonary septum
aortic
arch
brachiocephalic
trunk
left subclavian
artery
right
pulmonary
artery
left
pulmonary
artery
A
B
aorta
pulmonary
trunk
aortico-pulmonary
septum
94
pulmonary
trunk
aorta
direction
of the
blood flow
Figure 12.7 Septation of the conus cordis and the truncus arteriosus into the aortic
trunk and pulmonary trunk. The spiral arrangement of the aortico-pulmonary septum
ensures that the aortic trunk becomes continuous with the fourth aortic arch arteries and the
pulmonary trunk communicates with the sixth aortic arch arteries. Modified from Moore et al.
(2013).
12.4.7. Development of aortic and pulmonary valves
The system of valves, the atrioventricular valves and semilunar valves, develops for
rectification of the blood flow.
The left atrioventicular valve has anterior and posterior leaflets and is termed the
bicuspid or mitral valve. The right atrioventricular valve has a third, small, septal cusp and
thus is called the tricuspid valve. The valve leaflets are attached to the ventricular walls by
thin fibrous chords - the chordae tendineae, which insert into small muscles attached to the
ventricle wall - the papillary muscles. These structures are sculpted from the ventricular wall
(see below in this chapter).
Once the endocardial cushions fuse and divide the common atrioventricular opening into the
left and right openings, the left and right atrioventricular valves form from the left and right
endocardial cushions. (Fig. 12.8 A) Cavitation of the muscular layer immediately beneath the
mesenchymal thickening and re-modelling of underlying tissue contribute to the formation of
the cusps and papillary muscles. (Fig. 12.8 B, C, D)
The semilunar valves, aortic and pulmonary, which are necessary for prevention of
backflow of blood into the left and right ventricles, develop from three swellings of
subendothelial mesenchymal tissue at the outlet of aortic and pulmonary trunks. Thus the
primordial semilunar valve consists of a mesenchymal core covered by endocardium.
Excavation and the thinning of the valve tissue create the final valve shape.
The mechanisms of valve remodelling in these final steps in both the atrioventricular and
semilunar valves are not fully understood yet, and are thought to involve apoptotic pathways.
The wall of primitive cardiac tube consists of two layers. The inner endothelial layer
presents the base of endocardium. The outer layer originates from the epimyocardial plate.
The superficial cells of epimyocardial plate line up to the one layer of epicardial mesothelium.
The deeper cells multiply, elongate and myofibrils form in their cytoplasm. Individual cells
arrange to the trabecules forming the myocardium. Outer portion of myocardium closer to
epicardium is little denser and gives rise to the myocardium of atria and ventricles. Inner
portion of myocardium is looser and presents a base of mm. papillares and septomarginal
trabecula (moderator band). Originally continuous layer of myocardium is later interrupted at
the interface of atrium and ventricle by the fibrous base of future heart skeleton.
12.4.8. Development of the conducting system of the heart
A portion of the myocardium differentiates into a conducting heart system. These
specialised myocardial cells are responsible for initiation and conduction of the electrical
impulses which regulate the rate of cardiac contractions. They function as peacemakers.
The first peacemaker is located in the right horn of sinus venosus. When the right horn is
incorporated into the right atrium this specialised tissue is referred as the sino-atrial node.
The next node of specialised cardiomyocytes, the atrioventricular node, is located in the
septum intermedium. From this node specialised atypical fibers formed by modified
cardiomyocytes grow, forming the interventricular bundle which conducts impulses to the
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musculature of ventricles – bundle of His. The bundle of His splits into two branches in the
interventricular septum, the left bundle branch for the left ventricle and the right bundle
branch for the right ventricle. The two bundle branches give rice to the terminal portion of
conducting system, individual fibers penetrating within the musculature of ventricles to the
subendocardial layer – Purkinje fibers. They stimulate individual groups of cells to contract.
B
A
B
2
1
3
7
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Figure 12.8 Development of atrioventricular valves. 1 – atrioventricular canal, 2 – superior
and inferior endocardial cushions, 3 – left and right endocardial cushions, 4 – septum
intermedium, 5 – right atrioventricular canal, 6 – left atrioventricular canal, 7 – ventricle, 8 –
cavities in the myocardium, 9 – muscular cords, 10 – atrioventricular valves, 11 – chordae
tendinae, 12 – papillary muscles. Modified from McGeady et.al. (2006). Modified from
Sadler (2006).
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12.5. Development of the arterial system
The dorsal aortae fuse with the cardiogenic tube. (Fig. 12.3) As a result of the cranio-caudal
folding the cranial portions of dorsal aortae form arches which are located laterally to the
foregut. With surrounding mesenchyme aortic arches form the first pharyngeal (branchial)
arches. Each pharyngeal arch receives its own cranial nerve and its own artery. The aortic
arches develop in parallel with increasing number of somites sequentially.
Finally there are six arterial arches between the dorsal and ventral aortae on each side.
The junction of ventral aortae with the truncus arteriosus is dilated portion named
aortic sac. Pairs of arch arteries pass through the arches joining the dorsal aortae before their
fusion. The unpaired more caudal portion of the dorsal aorta develops into the thoracic and
abdominal aorta. Common dorsal aorta gives rise to the segmental arteries and to the aa.
omphalomesentericae, aa. umbilicales, and aa. mesonephridicae. The most caudal portion,
which remains paired, develops into the internal and external iliac arteries and their
extensions and unpaired median sacral artery continues caudally.
Figure 12.9 Ventral view (A) and lateral view (B) of the six pairs of aortic arches
12.5.1. Aortic arches and their derivatives
Six pairs of aortic arches develop. Whereas all six arches remain functional in fish, in
mammals the first and second pairs of arches have largely atrophied and the fifth arch either
doesn´t develop at all (cattle) or remains rudimentary (pig, horse).
The third, fourth and sixth aortic arches give rise to components of the developing
circulatory system.
In the different mammalian species, due to relatively long neck and the heart movement
specific variations in formation of aortic arches are observable. The next description is typical
for cattle. (Fig. 12.10)
The first aortic arches largely degenerate, but the small portions remain and form the
left and right maxillary arteries, extensions from the external carotid arteries.
As well the second aortic arches undergo atrophy, but the small remnants persist as
the hyoid and stapedial arteries.
The third aortic arches lose the contact in its dorsal part with the fourth arches and
the cranial portions of the dorsal aortae form the internal carotid arteries (aa. carotidae
internae). The ventral aortae, extending cranially, develop into the common carotid arteries
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(aa. carotidae communis) continuing cranially into the external carotid arteries (aa.
carotidae externae).
The fourth aortic arches persist but they develop differentially on the right and the
left side. The right arch forms the final right subclavian artery (a. subclavia dextra) and
brachiocephalic trunk (truncus brachiocephalicus). The dorsal portion of forth right arch
atrophies. The left arch forms the base of aortic arch (arcus aortae) from which left
subclavian artery (a. subclavia sinistra) emanates.
The sixth aortic arches form pulmonary arteries (aa. pulmonales) from their ventral
portions. The dorsal portion of the left arch persists as a shunt, the ductus arteriosus Botalli,
which links the pulmonary artery with the dorsal aorta. At birth the lumen of the ductus
arteriosus is obliterated and this structure persists as the ligamentum arteriosum. The dorsal
portion of sixth right arch atrophies.
As explained above (septation of cono-truncus) two different outflow channels develop in the
truncus arteriosus - ascending aorta and pulmonary trunk. The channel giving rise to
ascendent aorta, arising from the primitive left ventricle, supplies blood to the derivatives of
the third and fourth aortic arches and the ventral and dorsal aortae. The channel for the lung
circulation, arising from the primitive right ventricle, supplies the sixth aortic arches. The
sixth aortic arch regresses on the right side but on the left one develops into the pulmonary
trunk, which remains connected to the aortic arch with ductus arteriosus Botalli.
AORTIC ARCH SYSTEM IN BIRDS
In contrast to mammals, in birds the left systemic arch (IV) does not develop, and all functions are
carried out by the right systemic arch. The subclavians arise from the internal carotids instead of the
dorsal aorta. Arch III remains as a shunt between the external and internal carotids. With loss of the
left systemic arch, the left ductus caroticus loses its posterior connection, and usually becomes
functionally modified. In most instances this is followed by a similar disconnection of the right ductus
caroticus. The latter, however, frequently retains its connection between the carotid and systemic
arches and remains as a patent vessel. The proximal (ventral) parts of the left and right sixth aortic
arches become the left and right pulmonary arteries, joining the pulmonary trunk with lungs, while the
distal (dorsal) parts atrophy (ductus arteriosus Botalli doesn´t develop.)
12.5.2. Branches of dorsal aorta
The dorsal aortae (initially paired, later fused into a single vessel) give rise to dorsal, lateral
and ventral segmental arteries.
Dorsal (parietal) branches are paired and emanate between individual somites (metameric
arrangement) from the most cranial somites back to the sacral region. They run dorsally and
give rise to dorsal and ventral rami. A dorsal branch supplies the dorsal body region and the
neural tube and a ventral branch supplies ventral body wall. A series of longitudinal
anastomoses develop between the segmental arteries. In the cervical region, the first six
intersegmental arteries lose the connection with dorsal aortae, their dorsal portions and dorsal
aorta atrophy, and ventral portions form anastomosis, ventral cervical artery (a. colli
ventralis), which arises from the seventh intersegmental artery and the base of truncus
thyreocervicalis. The seventh intersegmental arteries supply the developing forelimb buds. In
the thoracic region the anastomoses of rami dorsales form truncus costocervicalis and
anastomoses of rami ventrales form internal thoracic artery (a. thoracica interna). The
intersegmental arteries persist as the intercostal arteries (aa. intercostales). The intersegmental
arteries in the lumbar region form the lumbar arteries (aa. lumbales) and the longitudinal
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anastomosis of rami ventrales form a. epigastrica caudalis. The most caudal lumbar
intersegmental arteries supply the pelvic limb buds and form the external iliac arteries.
Figure 12.10 Development of the aortic arches and their derivatives (ventral view, left
side - L, right side - R). 1 – 6 – aortic arches, 7 – a. vertebralis dextra, 8 – a. axillaris dextra,
9 – truncus arteriosus, 10 – aorta descendens, 11 – ramus pulmonalis dexter, 12 – ramus
pulmonalis sinister, 13 – ductus arteriosus Botalli, 14 – a. pulmonalis, 15 – aa. carotis
communis, 16 – a.carotis interna, 17 – a. brachiocephalica, 18 – arcus aortae. Modified from
Horký et al. (1984).
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Lateral branches don´t have segmental arrangement and they emanate from the unpaired
portion of aorta. They supply organs, which develop from the urogenital ridge (plica
urogenitalis). With the further development of the urogenital system these arteries develop
into the ovarian, testicular, renal and adrenal arteries.
Ventral (visceral) branches are initially paired and are associated with the yolk sac and
allantois. The most cranial pair, omphalomesenteric (vitelline) arteries, arises from the
unpaired portion of the dorsal aorta and supplies yolk sac. Later the left vitelline artery
involutes and disappears and the right one develops into the coeliac artery (a. coeliaca) and
mesenteric arteries (a. mesenterica cranialis at caudalis). From the caudal portion of the
dorsal aorta the umbilical arteries form which supply the allantois and thus the placenta.
Postnatally thin aa. iliacae externae emanate from the proximal portions of umbilical
arteries. Later they form huge arterial stems for pelvic limbs. The distal parts of umbilical
arteries give rise to the internal iliac artery (a. iliaca interna) for the pelvic wall and the
cranial vesical artery (a. vesicalis cranialis). The dorsal aorta terminates as unpaired sacral
artery (a. sacralis mediana) which continues to the base of the tail (a. caudalis mediana).
12.6. Development of venous system
The venous system forms concurrently with the arterial system in a similar manner. Basically,
three pairs of major veins develop in early embryo: the omphalomesenteric or vitelline
veins, the umbilical veins and the cardinal veins.
12.6.1. Vitelline veins
The paired vitelline veins differentiate from the mesenchyme of splanchnopleure and convey
the blood from the yolk sac through the umbilicus and ventral mesenterium (alongside the gut
run cranially) and through the septum transversum to the sinus venosus of developing heart.
The cell cords of developing liver extend towards the septum transversum which leads to
formation of venous plexus from the middle segments of the vitelline veins. This vascular
plexus becomes incorporated to the developing liver parenchyma forming the system of liver
sinusoids. The fate of cranial segments of the vitelline veins is different. The left cranial
segment which enters the left horn of the sinus venosus atrophies. The right cranial segment
of the vitelline vein persists and develops to the hepatocardiac portion of the caudal vena
cava, which conveys blood from the liver into the right horn of the sinus venosus. Two
anastomoses form between caudal segments of vitelline veins. The cranial anastomosis is
located dorsal to the midgut and the caudal anastomosis is located ventral to the midgut. At
the point of cranial anastomosis cranial and caudal mesenteric veins and gastrolienal vein join
with the left vitelline vein. During the next development in consequence of the stomach
rotation gradual alteration in the patency of segments of the left and right vitelline veins and
re-direction of blood flow occurs. The non-patent portions atrophy and the portal vein
draining the gut and its derivatives is formed from the caudal anastomosis between the right
and left vitelline vein and the caudal segment of the right vitelline vein.
12.6.2. Umbilical veins
The paired umbilical veins convey blood from the allantois through the umbilical cord,
through the septum transversum and enter the sinus venosus. As the result of liver
enlargement the umbilical veins become subdivided into cranial, middle and caudal segments,
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each with a different developmental fate. Because of the developing liver expands laterally,
the middle portions of umbilical veins initially passing the liver are incorporated into the
hepatic parenchyma and contribute to the formation of the liver sinusoids. The cranial
segments of the left and right umbilical veins atrophy. The caudal segment of the right
umbilical vein atrophies and the caudal segment of the left umbilical vein enlarges and
conveys all oxygenated blood from the placenta to the embryonic liver. Initially, blood flows
only through the system of liver sinusoids to reach the right horn of the sinus venosus.
Subsequently, a venous shunt, ductus venosus Arantii develops between the left umbilical
vein and the cranial segment of the right vitelline vein. The ductus venosus persists up to birth
in ruminants and carnivores but atrophies during the gestation in horse and pig. The remnant
of atrophied left umbilical vein post-partum is ligamentum teres hepatis. In the embryo and
foetus, the left umbilical vein is suspended in the ligamentum falciforme.
12.6.3. Cardinal veins
The paired cranial cardinal veins (vv. cardinales craniales) drain blood from the head, neck
region and the cranial portion of the thorax while the caudal cardinal veins (vv. cardinales
caudales) are found dorsolateral to the mesonephros and carry blood from the caudal portion
of the body wall and the mesonephros. The cranial and caudal cardinal veins on the left and
right sides fuse forming the left and right common cardinal veins (ductus venosus) which
open to the sinus venosus.
The cranial cardinal veins continue to develop and form 3 plexuses which give rise to brain
sinuses, veins of cranial bones and veins of skin. Moreover, cranial to the heart, the right and
left cardinal veins join with ipsilateral subclavian vein (v. subclavia) draining forelimbs and at
this point become connected by an precardinal anastomosis. Finally the cranial cardinal veins
and precardinal anastomosis give rise to the right and left external and internal jugular veins
(v. jugularis externa at interna), brachiocephalic veins (v. brachiocephalica dextra at sinistra)
and cranial vena cava.
The caudal cardinal veins give rise to subcardinal veins which drain the developing
mesonephros and the supracardinal veins draining the dorsal region of the body wall. In
addition both caudal cardinal veins join together forming iliac anastomosis. At this point they
receive the external and internal iliac veins and vena sacralis mediana.
The caudal vena cava arises from the combination of atrophy and anastomosis of the right
vitelline vein, the caudal cardinal veins and the supracardinal veins.
The azygos veins develop from the cranial portions of the right and left cardinal and
supracardinal veins.
12.7. Blood circuit development
Evolutionary older type is vitelline circuit which is succeeded by the placental circuit.
Vitelline circuit is not important in mammals. Rudimentary the vitelline circuit develops in
horse, carnivores and rabbit where the yolk sac temporarily grows together with chorion
forming choriovitelline placenta. Thus the yolk sac enables provisionally take nutrients from
the uterus mucosa.
Placental circuit enables to take nutrients and oxygen from the mother blood. The oxygenrich blood reaches the developing embryo via the left umbilical vein and de-oxygenated blood
return back through the two umbilical arteries.
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12.7.1. Fetal circulation
The placenta is an organ where gaseous exchange, nutrient uptake and waste elimination
proceeds. The oxygenated blood reaches the embryo through the umbilical veins. Initially
these veins are paired but only the left one enters the embryo. The right umbilical vein
between the umbilicus and the liver atrophies (see above).
The left umbilical vein runs towards the liver where most of oxygenated blood bypasses
hepatic sinusoids and flow directly through ductus venosus Arantii to the caudal vena cava.
Only a small volume of blood passes through the hepatic sinusoids and mixes with
deoxygenated blood from the portal vein. This blood also enters the vena cava. Thus in caudal
vena cava the blood from the liver and caudal portions of the body, with lower concentration
of oxygen, mixes with oxygenated blood from the ductus venosus and enters the right
atrium. Here it is guided towards the foramen ovale by the valve in the caudal vena cava
(Eustachian valve) and the lower margin of foramen ovale, crista dividens. The pressure in the
right atrium is greater than in the left one. Thus most of relatively oxygenated blood enters the
left atrium and only a small fraction remains in the right atrium, mixes with the deoxygenated
blood from cranial vena cava and continues through the right atrioventricular foramen into the
right ventricle.
The blood from the right ventricle is pumped to the pulmonary trunk, where due to the high
pressure in the foetal lung circulation, the greater volume passes through the ductus arteriosus
Botalli to the caudal aorta.
In the left atrium, the relatively oxygenated blood received through foramen ovale mixes with
minimal amount of deoxygenated blood which arrives from the inactive lungs by the way of
pulmonary veins. Subsequently, this blood enters through the left atrioventricular foramen the
left ventricle and thence aorta. Since the first aortic branches, the coronary arteries and
brachiocephalic arteries for heart muscle and brain come off. Most of the blood in the aorta is
returned to the placenta for oxygenation through umbilical arteries. Branches from the caudal
aorta supply the thoracic and abdominal organs. (Fig. 12.11)
12.7.2. Changes in circulation at birth
The rupture of umbilical cord results in increasing level of carbon dioxide in the
blood. This stimulates receptors in the respiratory centrum in the medulla oblongata and thus
the first inspiration. The inspiration expands collapsed lungs, the blood inflow through
pulmonary arteries increases. The higher pressure in the left atrium compresses the thin
septum primum against the septum secundum and closes the foramen ovale. Thus the blood
that has been oxygenated in the lungs flows into the left ventricle and is expelled to the aorta.
After the rupture of the umbilical cord contraction of the smooth muscle and the
elastic fibers in the tunica media closes the lumina of the arteries and prevents bleeding.
Concurrently, reflexive contraction of the musculature of the wall of the ductus venosus
Arantii closes this foetal shunt. This closure becomes permanent after two to three weeks.
The ductus arteriosus Botalli closes reflexively, immediately after birth. Thus all
blood is directed through the pulmonary arteries to the functioning lungs. Although functional
closure occurs quickly, anatomical closure occurs gradually during the first year of life in
most species of domestic animals. The obliterated ductus arteriosus Botalli persists as the
ligamentum arteriosum, the obliterated left umbilical artery as the ligamentum teres
hepatis (see above), the obliterated umbilical arteries as the ligamentum teres vesicae and
the closed foramen ovale remains visible as the fossa ovalis.
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Figure 12.11 Fetal blood circuit. 1 – placenta, 2 – v. umbilicalis, 3 – liver, 4 – ductus
venosus Arantii, 5 – v. cava caudalis, 6 – v. pulmonalis, 7 – a. pulmonalis, 8 – foramen ovale,
9 – v. cava cranialis, 10 – v. jugularis, 11 – a. carotis communis, 12 – ductus arteriosus
Botalli, 13 – aorta, 14 – a. coeliaca, 15 – a. mesenterica cranialis, 16 – a. umbilicalis, 17 – v.
portae. Modified from Horký et al. (1984).
12.8. Development of lymphatic vessels and lymph nodes
Shortly after the establishment of the cardiovascular system, lymphatic vessels develop from
mesoderm by the process of vasculogenesis and angiogenesis. The embryonic lymphatic
endothelial cells are generally considered to arise from veins by endothelial sprouting. Firstly
primary lymphatic sacs develop and the next budding gives rise to capillary networks
permeating tissues and organs.
Initially, the lymphatic system appears as six primary lymph sacs. Paired jugular sacs
develop lateral to the internal jugular veins, followed by the single retroperitoneal sac on the
dorsal body wall at the root of the mesentery in the abdominal cavity. An additional sac, the
cisterna chyli, develops dorsal to the retroperitoneal sac at the level of the dorsal aortae and
the paired posterior or iliac lymph sacs also develop at the same time at the junction of the
iliac veins. (Fig.12.12)
Lymphatic vessels draining the head, neck and fore-limbs arise from the jugular sacs.
Drainage of lymph from the pelvic region and hind-limbs is through iliac sacs, while the
retroperitoneal sac and cisterna chyli drain the viscera. Two large lymphatic vessels join the
cisterna chyli with the jugular lymph sacs. Anastomosis between these two vessels gives rise
to a plexus of lymphatic vessels. From the combination of fusion, atrophy and remodelling of
these vessels, the thoracic duct is formed. (Fig.12.12)
Finally the thoracic duct opens into the right jugular vein and other connection between the
lymphatic system and the venous system atrophy. In conclusion the lymphatic system is oneway transit system, consisting of tissue capillaries, collecting vessels and ducts and draining
the venous circuit through the jugular vein or the cranial vena cava.
The lymph nodes develop from mesenchyme by the accumulation of mesenchymal cells
around, firstly the sacs, later the lymphatic vessels. Mesenchymal cells differentiate to the
reticular cells producing reticular fibers and amorphous substance. The lymphatic vessels are
converted to the network of lymphatic sinuses. Developing parenchyma is settled by
differentiated lymphocytes from the thymus and the bone marrow. The capsule is also
mesenchymal in origin.
The lymph nodes are inserted into the course of the collecting lymph vessels and serve as the
filters of the lymph before its return to the blood stream. The nodes tend to agglomerate in
groups, lymph centres. For example the medial retropharyngeal lymph centre cleans all the
lymph from the head, the deep cervical lymph centre receives the lymph from the neck or
axillary lymph centre receives lymph from the thoracic limb and cranial mammary gland.
Some lymphoreticular organs also develop in connection with internal body surfaces in the
form of the mucosa-associated lymphoid tissue (MALT). The components of MALT are the
palatine tonsils or Payer´s patches of the gut.
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12.9. Development of haemolymphonodi
The lymphonodi hemales formation begins later then the differentiation of lymph nodes in the
cattle and small ruminants. They consist of lymphoreticular tissue, accumulated around the
blood sinusoids.
R
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Figure 12.12 Development of the lymphatic vessels and lymph nodes. Ventral view, R –
right side, L – left side. 1 – jugular lymph sac, 2 – internal jugular vein, 3 – cranial vena cava,
4 – anastomosis, 5 – thoracic duct, 6 – cisterna chyli, 7 – retroperitoneal lymph sac, 8 –
posterior lymph sac, 9 – right lymphatic duct, 10 – final thoracic duct, 11 – lymph nodes, 12 –
dotted lines indicate involuted structures. Modified from Carlson (2004).
12.10. Development of spleen
The spleen is a lymphatic (lymphoreticular) organ, which develops in close relation to the
development of the stomach. The mammalian spleen develops as an aggregation of
mesenchymal cells and coelom epithelium cells in the dorsal mesogastrium. As the dorsal
mesogastrium and stomach rotate to the left, the spleen primordium is also drawn to the left
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and becomes apposed to the greater curvature of the stomach to which is connected by the
duplicature of the dorsal mesogastrium, the gastro-splenic ligament. (Fig. 13.14)
The mesenchyme differentiates to the splenic capsule and trabecules and also connective
tissue of the proper parenchyma. Within the second trimester splenic artery (a. lienalis), which
derives from a branch of the caudal aorta - celiac artery, enters the spleen and the complex
vascular structure of the red pulp is formed. Later, after the establishment of the
haemopoietic activity in the bone marrow, the organ is settled by B and also T lymphocytes,
the white pulp is created and the spleen becomes a functional lymphatic organ.
The spleen functions as a haemopoietic centre until the third trimester of foetal life (see
Chapter 12, the hepatolienal period of haemopoiesis), but it retains definite haemopoietic
potential throughout adult life.
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13 DIGESTIVE SYSTEM
By the reason of the craniocaudal and lateral folding of the trilaminar germ disc, the primitive
yolk sac is divided to the upper part, an intra-embryonic tube and the lower part, an extraembryonic yolk sac. Both compartments initially widely communicate at the developing
umbilicus. Later this opening becomes narrower and as the vitello-intestinal duct persists as
long as the yolk sac is present. The intra-embryonic tube, referred as the primitive gut or
archenteron is formed by one layer of endodermal cells and splanchnic mesoderm
(splanchnopleure).
The primitive gut is divided into three parts. The cranial portion formed within the head fold
is referred as the foregut, the part formed within the caudal fold is termed the hindgut and
the middle portion, which is continuous with the yolk sac, is named the midgut.
The cranial blind end of the foregut is apposed to an ectodermal depression in the developing
head region, the stomodeum, which later forms the oral cavity. A similar ectodermal
depression, the proctodeum, in the caudal region of the embryo enters in contact with the
blind end of the hindgut.
The ecto-endodermal membrane, which separates the stomodeum and the foregut, is called
the oropharyngeal membrane. The membrane separating the hindgut and the proctodeum is
termed the cloacal membrane. Later both membranes decay, the oral cavity becomes
continuous with the foregut and the hindgut opens to the proctodeum, which develops to the
anus.
The foregut gives rise to the pharynx and its derivatives, pharyngeal arches, pouches and
clefts, the respiratory diverticulum, further the oesophagus, the stomach as well as the
liver and the pancreas.
The midgut develops to the small intestine (duodenum, jejunum and ileum).
The hindgut forms the large intestine and also the allantois. (Fig. 13.1)
The primitive gut is suspended dorsally and anchored ventrally by mesenteries, duplicatures
of the peritoneum developed from the mesoderm. The dorsal mesentery extends from the
caudal end of developing oesophagus to the cloacal region and gives rise to the greater
omentum (omentum majus). The ventral mesentery atrophies, leaving the gut, becomes
restricted to the caudal portion of the oesophagus, the stomach and the duodenum and gives
rise to the lesser omentum (omentum minus). The developing liver grows into the lesser
omentum and one part of the ventral mesentery forms the falciform ligament carrying the left
umbilical vein from the umbilicus to the liver (see Chapter 12, „Development of umbilical
veins“). The absence of the ventral mesentery caudally allows the gut to elongate and undergo
partial rotation.
Numerous neural crest cells migrate to the developing digestive tube and form the submucosal
and mesenteric ganglions.
The primitive alimentary tube is composed from the endoderm and splanchnic mesoderm. The
epithelium of the digestive tube and all its glands derive from endodermal lining while the
splanchnic mesoderm gives rise to the smooth muscle and connective tissue of the tract.
13.1. Primary oral and nasal cavities
The primitive oral cavity develops from the ectodermal invagination in the developing head
region, the stomodeum. After the pharyngeal membrane regression ectodermal lining of
primitive oral cavity becomes continuous with the endodermal lining of the primitive gut.
The first recognizable facial structures which surround stomodeum are the frontonasal
prominence dorsally and the paired maxillary and mandibular prominences laterally and
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9
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III
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2
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Figure 13.1 Derivatives of the primitive gut. I - foregut, II - midgut, III – hindgut.
1 - stomodeum, 2 - primordium of the thyroid gland, 3 - oro-pharyngeal membrane, 4 pharynx and pharyngeal pouches, 5 - respiratory diverticulum, 6 - primordium of the
oesophagus, 7 - primordium of the stomach, 8 - liver bud, 9 - pancreatic buds, 10 primordium of the small intestine, 11 - primordium of the caecum, 12 - primordium of the
large intestine, 13 – primordium of the urinary bladder on urachus connecting to allantois, 14
– cloacal membrane, 15 – vitelline duct, 16 – allantoic duct. Modified from Sinowatz and
Rűsse (2007).
ventrally. The maxillary and mandibular prominences develop from the first pharyngeal
arches bilaterally (see later). The ectoderm of the frontonasal prominence thicken up to the
nasal (olfactory) placodes and subsequently, the medial and lateral nasal prominences
(processes) develop at each side of the nasal placodes. The nasal (olfactory) placodes deepen
to the nasal pits and gradually invaginate to the underlying mesenchyme, forming nasal
canals which fuse into the primitive nasal cavity. This primitive nasal cavity is separated
from the primitive oral cavity by the oronasal membrane. (Fig. 13.2) Consequently, the
caudal aspects of the oro-nasal membrane undergo regression and the primitive oral and nasal
cavities communicate widely by the primary choanae. The rostral remnant of the oro-nasal
membrane forms primary palate.
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Figure 13.2 Development of the oral and nasal cavity (median section). 1 – stomodeum,
2 – nasal placode, 3 - brain vesicle, 4 – mandibular prominence, 5 – foregut, 6 – nasal pit,
7 – frontonasal prominence, 8 – maxillary process (primary palate), 9 – primary oral cavity,
10 – primary nasal cavity, 11 – oronasal membrane, 12 - primary choana, 13 – tongue,
14 – lung bud, 15 – oesophagus, 16 – secondary nasal cavity, 17 – secondary palate,
18 – choana, 19 - secondary oral cavity, 20 – trachea. Modified from McGeady et al. (2006).
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13.2. Craniofacial development
As mentioned above, the face is initially formed by 5 mesenchymal swellings or
prominences: 2 maxillary and 2 mandibular (right and left) prominences and frontonasal
prominence. The maxillary prominences increase in size, extend medially and fuse with
lateral nasal prominences. A deep groove called the nasolacrimal groove forms between the
maxillary and lateral nasal prominences on either side of the developing nose. Most of the
groove is obliterated with fusion of the maxillary and lateral nasal prominences, but a small
portion persists as the lacrimal sac and nasolacrimal duct, connecting the conjunctiva of the
developing eye with the nasal cavity. Continued inward growth of the maxillary prominences
also pushes the two medial nasal prominences to one another such they fuse to form the
midline of the nose, philtrum of the upper lip and the intermaxillary segment
(premaxilla). (Fig. 13.3) The final shape of the upper lip depends upon the level of midline
fusion between the medial nasal prominences. The incomplete fusion leaves the median
groove, the philtrum (carnivores). The complete fusion results in a continuous upper lip
(horse, cattle, pig).
Finally, the maxillary prominences fuse with the intermaxillary segment.
The mandibular prominences grow together to form a single mandible.
The superior portion of the frontonasal prominence grows and extends to form the forehead.
The maxilla and the mandibula (nasomaxillary complex) are formed completely by
intramembranous ossification. The first ossification centrum appears in premaxilla, the next
bilaterally for the maxilla proper.
13.3. Palate
The secondary palate develops from the palatine processes extending from the maxillary
bones, and the primary palate extending from the intermaxillary segment (premaxilla)
caudally. (Fig. 13.4) The palatine processes grow firstly ventrally from the lateral walls of the
primary nasal cavity on either side of the tongue, which at this stage of development projects
into the primary nasal cavity. (Fig. 13.5) With growth and expansion of the mandible the
tongue moves down, allowing the palatine processes to grow towards the middle line and fuse
to form the secondary palate. (Fig. 13.4, Fig. 13.5) The rostral area of the secondary palate
fuses with the primary palate (maxillary process) extending from the premaxilla.
At the site of fusion of the maxillary processes with the secondary palate small spaces retain,
the incisive foramina (Fig. 13.4), from which paired incisive ducts develop.
Associated with the formation of the palatine processes, a nasal septum develops and grows
ventrally from the roof of the nasal cavity. Fusion of the nasal septum with the secondary
palate divides the common nasal cavity into the left and right nasal cavity. The extent of
fusion between the nasal septum and the secondary palate influences the definitive form of
communication between the pharynx and the nasal cavities. In horses, the nasal septum fuses
with the secondary palate throughout its length so that each nasal cavity communicates with
the pharynx by a separate opening. In the other domestic animals, the fusion does not extend
to the caudal end of the secondary palate and both nasal cavities share a common opening to
the nasopharynx.
The palate bones develop by intramembranous ossification in the rostral two thirds, forming
the hard palate. The portion, which projects into the nasopharynx, dividing it to the nasal and
oral part, remains membranous, forming the soft palate.
110
Figure 13.3 Development of the facial structures related to the oral and nasal cavities.
Line D indicates the level of section in D. 1 – frontonasal prominence, 2 – maxillary
prominence, 3 – mandibular prominence, 4 – lateral nasal prominence, 5 – nasal placode,
6 – medial nasal prominence, 7 – stomodeum, 8 – nasal pit, 9 - lens placode, 10 –
nasolacrimal groove, 11 – intermaxillary segment, 12 – mandible. Modified from McGeady et
al. (2006).
Figure 13.4 Development of the secondary palate by the fusion of intermaxillary
segment with palate processes. 1 – intermaxillary segment, 2 – maxillary prominences,
3 – primary palate, 4 – lateral palatal processes, 5 – secondary palate, 6 – incisive foramen,
7 – median palatine suture (raphe palati)
111
1
A
B
3
2
C
D
D
i
g
6
3 u
r
e
7
1
4
3
.
5
5
D
e
v
e
l
o
p
m
e
n
t
o
f
t
h
e
s
e
c
o
n
d
a
r
Figure 13.5 yDevelopment of the secondary palate and formation of the secondary oral
p
and nasal cavities
(A – C). 1 - primary nasal cavity, 2 - maxillary prominence, 3 a
mandibular prominence,
4 - developing nasal septum, 5 – tongue, 6 - palate process, 7 l
developing concha,
8 - developing vomeronasal organ, 9 – secondary palate, 10 – primary
oral cavity, 11a – secondary nasal cavity, 12 – secondary oral cavity Modified from McGeady
et al. (2006). t
e
112
a
n
d
f
13.4. Oral cavity
The oral cavity develops from the stomodeum. Initially, the oral rima is markedly wide. (Fig.
13.3) Structures associated with the rostral region of the stomodeum are lined by ectoderm,
and the base of them is formed by the undifferentiated mass of mesenchyme, from which the
jaws develop. A thickened band of ectoderm on the occlusal surfaces of the developing jaws
forms upper and lower labio-gingival laminae. Subsequently, a loss of cells in the
intermediate portions of these laminae results in formation of the vestibulum oris between
the primordia of lips and gums. An epithelial thickening on the lingual surface of the gum
gives rise to the dental lamina (Fig. 13.6)
Lateral fusion between the upper and lower labio-gingival laminae results in development of
the cheeks and definitive oral aperture.
Figure 13.6 Development of the labio-gingival and dental laminae. 1 – ectodermal
epithelium, 2 - mesenchyme, 3 – labio-gingival lamina, 4 – dental lamina, 5 – lip, 6 –
vestibulum oris, 7 – cap-shaped dental bud, 8 – gum. Modified from Horký et al. (1984).
13.5. Teeth
All teeth have the same basic structure. They consist of enamel, which is produced by cells
originating in the ectodermal dental lamina, and dentin and cementum, which originate from
the underlying neural crest-derived mesenchyme. The majority of mammals have two forms
of dentition, deciduous teeth and permanent teeth. They are named diphyodonts. Deciduous
teeth are fewer in number and later, postnatally, they are replaced by the permanent teeth.
According to the position in the jaws, teeth morphology and function, the teeth of mammals
are also classified as incisors, canines, premolars and molars. Moreover, there are two main
types of teeth in domestic animals, brachyodont and hypselodont. A brachyodont tooth
consists of a crown, a neck and a root. A hypselodont tooth has a body and a root.
The dental lamina (Fig. 13.6) firstly gives rise to the cap-shaped dental buds of deciduous
dentition. The remnant dental lamina organises to the secondary dental lamina for the
permanent teeth dentition. The dental buds are temporarily connected with the dental lamina
by the stem. In ruminants, the dental buds establish throughout all the maxilla but in its future
incisive area they stay rudimentary.
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The teeth development is based on the interactions between the ectoderm of the dental lamina
and the underlying neural crest-derived mesenchyme. Ectodermal proliferations along the
length of the dental lamina give rise to the dental buds (dental primordia), which project to
the mesenchyme. The mesenchymal thickening, known as the dental papilla crushes into the
bud, which becomes cap-shaped. (Fig. 13.7 B)
The cap-shaped bud consists of an inner and outer layer of epithelial cells, outer and inner
enamel epithelium, and the stellate reticulum, interposed between them. This formation is
named the enamel organ. (Fig. 13.7 C)
As the dental cap grows deeper into the mesenchyme, it acquires a bell-shaped appearance.
The dental bud is still connected with the oral epithelium by a cord of cells.
Under to inductive influence of the dental papilla, a small group of ectodermal cells of the
inner epithelial layer located at the apex of the dental papilla form the enamel knot. (Fig. 13.7
D) The cells of enamel knot act as a signalling centre, which regulates the shape of the
developing tooth and specifies the site of cusp formation. In the development of teeth with
more cusps, more enamel knots are formed. The formation of the enamel organ and the
enamel knot reacts to the dental papilla, and adjacent mesenchyme differentiates into a
columnar epithelium formed by odontoblasts. These cells produce predentin, which forms
the layer between odontoblasts and inner enamel epithelium. The predentin is subsequently
mineralized by the crystals of hydroxyapatite and fluoroapatite and turned into the bone-like
dentin. The core of the dental papilla gives rise to the pulp cavity of the tooth, which is filled
with gelatinous connective tissue and carries blood vessels and nerves.
Stimulated by dentin, the inner enamel epithelium differentiates into a columnar epithelium
composed of ameloblasts. Ameloblasts produce the enamel, starting at the tip of the
developing tooth, which forms the layer outside the dentin. Due to the thickening of enamel
layer, ameloblasts withdraw peripherally and the stellate reticulum is reduced. Subsequently,
both layers of enamel organ epithelium appose and form dental cuticle (Nasmyth´s
membrane, adamantine membrane) covering the crown of dental primordium or newly
erupted teeth and abraded by mastication. (Fig. 13.7)
At the base of the cap-shaped enamel organ, the inner and outer enamel epithelia meet. From
their junction, the epithelium proliferates and extends deeper into the mesenchyme as the
tube-like root sheath (radicular epithelial sheath of Hertwig). The root sheath induces the
adjacent mesenchyme to differentiate into the odontoblasts that produce the dentin of the root.
There is no stellate reticulum, which supports differentiation of ameloblasts at the crown and
so the enamel epithelium never differentiates into the ameloblasts and the root of brachyodont
tooth is not covered with enamel. With thickening of dentin layer in the root, the pulp cavity
is gradually reduced in size and the narrow root channel is formed. Odontoblasts remain
active throughout life and due to the continuous production of predentin and dentin the size of
the dental pulp, which carries blood vessels and nerves, is reduced.
During the bell-shaped stage of development, the mesenchyme surrounding the developing
tooth condenses, forming a vascular mesenchymal layer, the dental sac. (Fig. 13.7 C, D)
Around the root, the inner layer of the dental sac differentiates into the cementoblasts,
producing bone-like substance cementum. Similarly like osteoblasts, cementoblasts are
enclosed within their matrix and become cementocytes. The middle layer of dental sac
around the developing root gives rise to tough collagen fibres, the periodontal ligaments.
From the mesenchyme of the outer layer of the dental sac differentiate osteoblasts, which
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give rise to bone of dental alveoli. Periodontal ligaments become anchored to the bone of the
alveolus and in the cementum covering the root.
Figure 13.7 Early stages in the formation of a deciduous brachyodont tooth.
A - dental bud, B - dental cap, C - bell shaped stage, D - primordium of tooth.
1 - dental lamina, 2 - oral epithelium, 3 - dental bud, 4 - dental papilla, 5 - epithelium of the
dental cap, 6 - stellate reticulum, 7 - outer epithelium of enamel organ, 8 - inner epithelium of
enamel organ, 9 - odontoblasts, 10 - dental sac, 11 - bud of permanent tooth, 12 – enamel
knot, 13 – dentin, 14 – blood vessel
115
dental
sac
epithelial root
sheath
primordium of
permanent tooth
enamel
oral epithelium
periodontal
ligament
primordium of
permanent tooth
Fig. 13.8. Final stage in the development of deciduous brachyodont tooth
116
The development of hypselodont teeth is similar in most aspects to that of described
brachyodont teeth. The differences are: 1) Enamel organ is longer and may exhibit folding on
its occlusal surface. This folding results in the formation of vertical ridges. 2) In addition the
enamel organ is not restricted to the crown of the tooth and so more the tooth becomes
covered by enamel. 3) Furthermore the dental sac differentiates into cementoblasts around the
complete tooth and so the enamel is covered with a layer of cementum (tusks in boar).
A horse's incisors, premolars, and molars, once fully developed, continue to erupt as the
grinding surface is worn down through chewing. Cup, star and spot are the structures that
appear at the occlusal surface of horse incisors. The cup is the centre of the infundibulum.
Wear of the occlusal surface causes the cup to get smaller and eventually disappears from all
lower incisors at about 8 years of age leaving the enamel spot in its place. The enamel spot is
the deepest part of the infundibulum. The dental star corresponds with the pulp cavity and
appears at 8 years of age in the first incisor. It begins as a dark line in front of the dental cup
and then changes to a large, round spot as the occlusal surface is worn further. It is still visible
after the cup and enamel spot have been worn away (Fig. 13.10)
Figure 13.9 Hypselodont tooth of horse. The structure of horse´s permanent incisor and
typical wear patterns. Modified from McGeady et al. (2006).
117
13.6. Salivary glands
The salivary glands develop as the solid epithelial ingrowths during the later stages of
embryonic development. The club shaped epithelial buds grow into the underlying
mesenchyme. The buds for large salivary glands repeatedly branch, form the lumen and
terminal portions give rise to secretory units, the acini. The ducts and glandular tissue are
derived from the oral epithelium while the interstitial connective tissue and capsule of the
gland are of neural crest-derived mesenchymal origin. Other epithelial ingrowths do not
ramify and give rise to a number of small diffuse salivary glands, which open into the oral
cavity and are named according to their location (labial, buccal, lingual, palatine and
pharyngeal).
13.7. Tongue
The tongue develops at the bottom of the oral cavity and at the floor of the primordial pharynx
by the proliferation of underlying mesoderm. Mesoderm originates from the ventral portions
of first four pharyngeal arches and the tongue primordium is invaded by myoblasts from
occipital myotomes. The first sign of tongue development are three prominences at the level
of the first pharyngeal arch; a medial prominence, referred to as the tuberculum impar, and
two rostro-lateral prominences, tubercula lateralia. (Fig. 13.10) The tuberculum impar and
tubercula lateralia give rise to the rostral two-thirds of the tongue, apex and body (apex and
corpus linguae).
Caudally, in the region of ventral portions of the second, third and fourth pharyngeal arches,
two prominences develop in median position, referred as the copula and eminentia
hypobranchialis. The copula later atrophies and is overgrown by the material from the rostral
portion of the eminentia hypobranchialis that forms most of the root of the tongue (radix
linguae).
Paired lateral lingual swellings fuse with each other and with tuberculum impar. The midline
fusion of the lateral swellings gives rise to the lingual septum and the lyssa in carnivores or
cartilago dorsi linguae in the horse. The line of fusion can be recognised at the surface of the
tongue in humans and carnivores by a medial groove. In ungulates, the medial lingual
prominence, tuberculum impar, significantly contributes to the dorsal prominence of the body
of the tongue. In cattle this prominence is especially large and is called torus linguae.
The epithelium covering the rostral two-thirds of the tongue is of ectodermal origin (originally
lining of stomodeum), while that of the caudal third is endodermally derived (originally lining
of primordial pharynx). At the interface of the ectoderm and the endoderm, between the
tuberculum impar and copula, endodermal ingrowth gives rise to the thyro-glossal duct
(ductus thyreoglossus), connecting the endodermal epithelium with the base of thyroid
gland. The line of fusion of both bases of the tongue (tuberculum impar and copula), has the
shape of upside down letter V and is termed sulcus terminalis linguae. At the top of V line
the shallow depression, foramen caecum, as the rudiment of ductus thyreoglossus is
observable.
The innervation of the tongue by the n. trigeminus, n. facialis and n. glossopharyngeus
proves the origin from three pharyngeal arches. The muscle of the tongue is derived from
occipital myotomes and is innervated by the hypoglossal nerve.
Axons from visceral afferent neurons induce the development of the lingual papillae. Firstly
fungiform papillae form, induced by axons of the facial nerve. Later axons from the
glossopharyngeal nerve induce the development of the vallate papillae and foliate papillae.
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A
2
2
1
I
3
4
II
III
5
IV
6
VI
B
2
2
1
I
4
3
II
5
III
IV
7
6
Figure 13.10 Development of the tongue. I –VI - pharyngeal arches, 1 – tuberculum impar,
2 – lateral lingual swellings, 3 – primordium of the thyroid gland, 4 – copula, 5 – eminentia
hypobranchialis, 6 – arytenoid swellings, 7 – laryngeal orifice. Pink arrow – structures
developed from the first pharyngeal arch giving rise to the apex and corpus linguae. Black
arrow – structures from which radix linguae develops. Modified from Sinowatz and Rűsse
(2007).
119
The filiform papillae arise from small outgrows of proliferating epithelium induced by the
underlying mesoderm. These papillae contain the nerve endings for sensation of pressure.
Accordingly the foliate papillae on the lateral aspect of the tongue are formed.
The taste buds development is induced by the interaction between the epithelial cells on the
papillae and gustatory neurons of cranial nerves (n. facialis, n, glossopharyngeus, and n.
vagus). Serous gustatory glands and other small salivary glands of the tongue develop from
the epithelial buds, which grow into the underlying mesenchyme.
13.8. Thyroid gland
The thyroid gland develops from the rostral portion of the foregut, the floor of primordial
pharynx, at the level of the first pharyngeal pouch. (Fig 13.10) The endodermal diverticulum
extends ventrally and caudally into the underlying mesenchyme. The blind end of this bud
becomes bilobar and occupies a position on the ventral aspect of the developing trachea. The
connection with the foregut, thyro-glossal duct (ductus thyreoglossus) becomes extinct.
Both lobes enlarge and move laterally, but they remain connected by the band of glandular
tissue, the isthmus. The amount of glandular tissue which persists in the isthmus is very
different in animal species. In human and pigs the isthmus forms the third medial lobe. In
cattle it is well defined band of glandular tissue, while in horses only thin stripe. In ruminants
the isthmus is replaced by a band of connective tissue and in dogs and cats the connection is
lost and the thyroid gland consists of two separately located lobes.
The endodermal cells of the thyroid diverticulum differentiate into cuboidal epithelial cells,
which organise into follicles and synthesize the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). Moreover, the thyroid primordium is invaded by the C cells or
parafollicular cells, which originate from the ultimo-branchial body developing from the
ventral portion of the fourth endodermal branchial pouch. Parafollicular cells secrete
calcitonin.
13.9. Pharynx and its derivatives
The pharynx develops from the most cranial portion of the foregut closely behind the oropharyngeal membrane, so that inner lining of the pharynx is of endodermal origin.
Development of the specific features of primitive pharynx, pharyngeal arches, begins at the
fourth week of gestation by the migration of neural crest cells into the developing head and
neck region. Aggregations of these cells, located between ectoderm and endoderm, give rise
to mesenchyme of the six pairs of pharyngeal arches. At the end of the first month of
gestation the first four well-defined pairs of arches can be detected like surface elevations on
the lateral aspects of the developing head and neck. The presence of rudimentary fifth and
sixth pharyngeal arches is not discernible on the surface. The fifth pharyngeal arch undergoes
atrophy, while the sixth arch fuses with the fourth arch, forming a fourth-sixth arch complex.
Each pharyngeal arch includes a muscle component derived from somitomeres, aortic arch
artery and a branch of a cranial nerve which supplies the arch musculature and provides
sensory innervation to the epithelia associated with the arch.
Just caudal to each arch, invaginations of surface ectoderm, known as external pharyngeal
clefts, develop. The pharyngeal clefts correspond with evaginations of the endoderm of the
lateral wall of the pharyngeal primordium, pharyngeal pouches. Where ectoderm of the cleft
and endoderm of the pouch enter in the contact with each other, obturatory membranes
(membranae obturantes) are formed. In fish, these membranes break down establishing
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communication between the oral cavity and exterior, the gills. Collectively, the pharyngeal
arches, clefts and pouches, are referred to as pharyngeal complex or apparatus. They give
rise to a number of organs.
pharyngeal
clefts
arches
tongue
buds
thyroid
diverticulum
pharyngeal pouches
1
1
1st
2nd
2
3
2
3rd
3
4
4
4th
Ectoderm
Mesoderm
Endoderm
esophagus
foramen
ceacum
tongue
thyroid
diverticulum
tubotympanic
recess
external
acustic
meatus
palatine
tonsil
cervical
vesicle
lateral parathyroid
bud from 3rd
pharyngeal pouch
thymus
medial
parathyroid bud
from 4th
pharyngeal pouch
ultimopharyngeal
body
Figure 13.11 Development of the pharyngeal clefts and pouches. Modified from Moore et
al. (2013).
121
13.9.1. Pharyngeal clefts
Only the first pair of pharyngeal grooves (clefts) contributes to the postnatal structures. The
ectoderm of the first pharyngeal cleft forms the epithelial lining of the external auditory
meatus. In mammals, the second arch extends caudally over the second, third and fourth cleft,
overlies them and closes an ectoderm-lined cervical sinus (later vesicle), a cavity in the neck,
which later disappears. (Fig. 13.11)
Branchial anomalies can present as cysts, sinuses, or fistulae. Cysts are remnants of the
cervical sinus without an external opening. Sinuses are the persistence of the cervical sinus
with its external opening, whereas a fistula also involves persistence of the branchial groove
with breakdown of the branchial membrane resulting in a pharyngocutaneous fistula.
13.9.2. Pharyngeal arches
The first pharyngeal arch, also referred to as the mandibular arch, consists of a dorsal
portion, the maxillary process, and a ventral portion, the mandibular process. These
symmetrical facial structures grow towards each other and fuse in the midline, enclosing an
invagination of ectoderm, the stomodeum. The maxillary processes give rise to the maxilla,
the zygomatic bone, a portion of the temporal bone and the hard palate by the
intramembranous ossification. The mandibular processes contribute to formation of lower
jaw, mandible, also through the intramembranous ossification. Inside each mandibular
process, there is a plate of cartilage, referred to as Meckel´s cartilage. Most of this structure
disappears, but the dorsal portions give rise to the incus and malleus of the middle ear.
The muscular derivatives of the first pharyngeal arch include the muscles of mastication, the
myohyoid, rostral belly of digastricus, tensor tympani and tensor veli palati.
The first pharyngeal arch and its derivatives are supplied by the trigeminal nerve (V).
The second pharyngeal arch (hyoid arch) is smaller than the first and contains Reichert´s
cartilage, remnants of which give rise to the stapes of the middle ear. The mesenchyme of
the second arch gives rise to some bones of hyoid apparatus (lesser horn and the upper
portion of the body of the hyoid bone and stylohyoid process of the temporal bone), to the
muscles of facial expression, as well as the stapedius, stylohyoid, caudal belly of digastricus
and auricular muscles.
The second pharyngeal arch and its derivatives are supplied by the facial nerve (VII).
The third pharyngeal arch. The cartilage of this arch gives rise to the greater horn and
lower part of the hyoid bone. Muscular derivatives include the pharyngeal muscle (m.
stylopharyngeus) and the arch and its derivatives are supplied by the glossopharyngeal nerve
(IX).
The fourth and sixth pharyngeal arches merge forming the fourth-six complex, which
gives rise to laryngeal cartilages (epiglottal, thyroid, cricoid and arytenoid cartilages, later
corniculate and cuneiform). More over the muscles of larynx develop from its mesenchyme
and the arches are supplied by the vagus nerve (X) (cranial and recurrent laryngeal branches).
13.9.3. Pharyngeal pouches
The first pharyngeal pouch. This pouch initially forms a diverticulum, so called
tubotympanic recess, which extends opposite to the first pharyngeal cleft. Only the thin
mesenchymal partition remains between ectoderm and endoderm and this wall gives rise to
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tympanic membrane (membrana tympani). The tubotympanic recess gives rise to the middle
ear cavity and auditory (Eustachian) tube. In horse, the auditory tube evaginates, forming
dilatations, the guttural pouches (diverticulum tubae auditivae). (Fig. 13.11, Fig. 13.12)
The second pharyngeal pouch. The endodermal epithelium of the second pharyngeal pouch
proliferates into the underlying mesenchyme, which later differentiates to the reticular stroma
of the palatine tonsil. The central parts of the epithelial invaginations break down, forming
the tonsillar crypts. However, the second pouch is partially obliterated by developing
lymphoid tissue in underlying mesenchyme, part of its cavity remains as the tonsillar sinus or
fossa tonsilaris.
The third pharyngeal pouch. Dorsal and ventral primordia develop from this pouch. (Fig.
13.11, Fig. 13.12) The dorsal primordium gives rise to the external parathyroid gland while
the ventral one forms a reticulated stroma (epithelial reticulum) of thymus, later invaded by T
lymphocytes derived from the bone marrow. The ventral primordium extends ventrocaudally
as far as the ventral mediastinum. During this migration a slim cervical portion and more
round thoracic portion are formed. Finally, the connection of the thymus to the pharyngeal
pouch is lost and two parts of initially bilateral organ fuse into a single structure located in the
cranial mediastinum. The capsule of the thymus develops by the thickening of the
surrounding mesenchyme, which also penetrates into the reticulum, forming septa and
separating individual lobules (lobuli thymi). At birth, the thymus is fully developed but it
starts to involute soon afterwards and involution becomes especially marked during puberty.
The fourth pharyngeal pouch. The fourth pharyngeal pouch also expands into dorsal and
ventral primordium. (Fig. 13.11, Fig. 13.12) The dorsal primordium develops into the
internal parathyroid gland which, like its external counterpart, also migrates caudally and
becomes located in the vicinity of the thyroid gland. The elongated ventral primordium
develops into an ultimopharyngeal or ultimobranchial body, which is later incorporated
into the thyroid gland. Its cells disseminate within the thyroid where the parafollicular cells or
C cells form.
The fifth pharyngeal pouch. This pouch is rudimentary structure, which becomes part of the
fourth pouch contributing to thyroid C cells.
The sixth pharyngeal pouch. Along with the fourth pouch contributes to the formation of the
musculature and cartilage of the larynx.
After the separation of pharyngeal derivatives the definitive pharynx is formed. The
pharyngeal glands develop from the epithelial buds, which grow into the mesenchyme.
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1
2 34
4
A
3 2
1
B
maxillary
process
mandibullar
process
1
branchial
clefts
2
1a
3 4
1
2a
2
c
d
3b
3
4
3a
4a
4b
C
D
Figure 13.12 Development of branchial pouches and branchial clefts. A – branchial
clefts, B – branchial pouches, C: 1 – external auditory meatus, 2, 3, 4 – the second, third and
fourth cleft inside cervical sinus, D: 1a - auditory tube and tympanic cavity, 2a – palatine
tonsil, 3a – external parathyroid gland, 3b – thymus, 4a – internal parathyroid gland, 4b –
ultimobranchial body
13.10. Oesophagus
The oesophagus, which at first is a wide and short tube, develops from the foregut and
extends from the developing pharynx to the spindle-shaped primordium of the stomach. In
connection with the elongation of the cervical region and the growth of thorax the oesophagus
increases in length and becomes narrower and embedded in the mediastinum. The dorsal
oesophageal hang, mesoesophageum dorsale, remains preserved, ventral hang disappears in
connection with the heart tube development.
In the early stages of development, oesophageal epithelium is columnar. Later, this
epithelium becomes stratified squamous in all species, with keratinisation evident in
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herbivores. Oesophageal glands develop from the epithelial buds, which grow into the
underlying mesenchyme. The distribution of the oesophageal glands is species-specific. The
mesoderm of splanchnopleure surrounding the endodermal epithelium gives rise to the
lamina propria and lamina muscularis mucosae, as well as other layers of the oesophageal
wall.
The tunica muscularis also displays species-specific differences. In the ruminants and dogs it
is composed of striated muscle, in the pig, the most caudal portions carry smooth muscle and
in the horse and cat the muscle of the caudal one-third is smooth. While the smooth muscle
cells have the mesenchymal origin, the striated muscle cells, myoblasts, apparently migrate
from the pharyngeal arches.
13.11. Stomach
The stomach develops like a fusiform dilatation of the caudal part of the foregut, which is
attached to the dorsal abdominal wall by the dorsal mesogastrium and to the ventral wall by
the ventral mesogastrium. Due to different structure of the stomach in most of animals and
the ruminants, in the following, the development of the simple stomach and ruminant complex
stomach will be described separately.
13.11.1. Simple stomach
The caudal part of the foregut enlarges and a swelling indicates where the stomach will form.
Because the dorsal region of the stomach grows more rapidly than the ventral region, the
dorsal surface becomes convex to form the greater curvature of the stomach and the ventral
surface becomes concave to form the lesser curvature. Two rotations of 90 degrees occur,
firstly around the cranio-caudal axis and then around the dorso-ventral axis. The first rotation
(90° anti-clockwise around a cranio-caudal axis) brings the dorsal portion of the developing
stomach to the left down and the ventral portion to the right up. (Fig.13.13) After the second
rotation (90° anti-clockwise around a dorso-ventral axis) the stomach is positioned
transversely with the caudal portion to the right and the cranial portion to the left. During the
next growth, the left-hand portion (cranial) develops into the cardia and the fundus, the
middle part into the corpus or body and the right-hand (caudal) portion into the pylorus.
(Fig. 13.14)
In consequence of the stomach rotation the dorsal mesogastrium becomes elongated (with
the spleen) and expands into a large fold along the ventral abdominal wall. This becomes the
greater omentum (omentum maius) which covers all the abdominal organs and encloses
saccate cavity, bursa omentalis. The ventral mesogastrium becomes the lesser omentum
(omentum minus). The proximal part of the ventral mesogastrium, which is in between the
stomach and the liver, gives rise to the ligamentum hepatogastricum and ligamentum
hepatoduodenale. The distal portion of the ventral mesogastrium initially develops into the
wide tentacle in between the liver and the septum transversum, which later fall into the
triangular, falciform and coronary ligament.
In domestic animals the lining of the gastric mucosa is firstly formed by simple columnar
epithelium, later exhibits species-specific regional differences. Simple columnar epithelium
persists throughout the stomachs of carnivores, while in horses and pigs stratified squamous
epithelium replaces columnar epithelium in the defined gastric regions. In those regions of the
stomach, where simple columnar epithelium persists, gastric glands develop from the
epithelial buds. The regions covered with stratified squamous epithelium are non-glandular.
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Figure 13.13 Rotation of the primordium of the stomach and formation of the lesser and
greater omentum. The first rotation is anti-clockwise around a cranio-caudal axis (A – D).
1 – aorta, 2 – primordium of the spleen, 3 – primordium of the stomach, 4 – primordium of
the liver, 5 – dorsal mesogastrium, 6 – ventral mesogastrium, 7 – hepatogastric ligament,
8 – falciform ligament, 9 – omental bursa, 10 - epiploic foramen
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cranially
E
F
left
right
caudally
5
3
1
1
4
2a
2
2b
7
6
7
F
90°
4
8
Figure 13.14 The second rotation of the primordium of the stomach anti-clockwise
around the dorso-ventral axis (E, F). 1 – spleen, 2 – stomach, 2a – cardia of the stomach, 2b
– pylorus of the stomach, 3 – epiploic foramen, 4 – liver, 5 – lesser omentum, 6 – omental
bursa, 7 – greater omentum, 8 – falciform ligament
13.11.2. Compound stomach of ruminants
At the beginning, the development of the gastric primordium in ruminants is the same as in
monogastric animals. This spindle-shaped primordial structure has a greater dorsal and lesser
ventral curvature and undergoes rotation to the left in a manner similar to that which occurs in
monogastric animals.
By the 34th day of gestation, in the cranial part of the greater curvature prominent blind sac, a
primordium of rumen and reticulum evaginates. Different growth of the rumino-reticular
primordium results in enlargement both in a cranial direction and to the left of the medial
plane. At the same time, an evagination develops in the cranial portion of the lesser curvature,
which forms an embryonic omasum. Caudally to this primordium, the proper gastric
primordium curves to the right and defines the future abomasum. (Fig. 13.15)
By about 37th day the rumino-reticular groove on the ventral surface of rumino-reticular
primordium develops, forming the distinct boundary between the rumen and reticulum. The
embryonic rumen continues to expand cranially and dorsally so that the primordium of the
liver is pushed to the right and the primordium of the reticulum is pushed to the left and also
cranially, thereby is attached to the diaphragm. The omasum, in consequence of the first
rotation, is positioned to the right side of abdominal cavity and abomasum to a ventral
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position. Only the abomasum participates in the second rotation of the stomach which results
in the ventral location of its greater curvature and dorsal location of its lesser curvature.
Figure 13.15 Development of the compound stomach in cattle embryos. 1 – oesophagus,
2 – common primordium for the rumen and reticulum, 3 – primordium of the rumen, 4 –
primordium of the reticulum, 5 – primordium of the omasum, 6 – primordium of the
abomasum, 7 – pylorus of the abomasum, 8 - intestine
128
By around the 40 days of gestation, the four compartments of the bovine stomach
primordium, namely rumen, reticulum, omasum and abomasum, are visible. The grooves and
pillars dividing the rumen into its dorsal and ventral sacs also appear at this stage.
During the first half of pregnancy, the relative sizes of the four compartments of the bovine
stomach system in the foetus are comparable with those seen in adult. Subsequently, in the
second half of pregnancy, the abomasum markedly develops, because it serves for milk
digestion during the first weeks after birth. Postnatally, in connection with the dietary change
from liquids to solids, the rumen, reticulum and omasum become functional and increase in
size.
Initially, all four compartments of the stomach system are lined by simple columnar
endodermal epithelium. The lining of the rumen, reticulum and omasum is replaced by the
stratified squamous epithelium; the abomasum retains columnar type of epithelium, in which
glands develop. Formation of the typical mucosal structures is firstly observable in the
abomasum, subsequently in omasum, reticulum and finely in the rumen, where ruminal
papillae are present at the end of the forth month of gestation.
13.12. Liver
The first morphologic sign of the embryonic liver is the formation of a hollow ventral
hepatic diverticulum from the caudal region of the foregut. The diverticulum divides into
cranial hepatic and caudal cystic part. (Fig. 13.16) The hepatic primordium grows cranioventrally into the ventral mesogastrium and extends into the septum transversum, where the
endodermal cells of the hepatic bud interact with cardiac mesoderm and mesoderm of the
septum transversum. Fibroblast growing factors (FGF) from the developing heart and BMP
signals from the septum transversum induce the proliferation of the hepatic endoderm. E.g.
hepatic growth factor is an example of a specific mesodermally derived growth factor.
The endodermal epithelial cells of the hepatic portion proliferate forming the plates of liver
cells, hepatocytes, and the epithelial lining of the intrahepatic part of the biliary apparatus.
Hepatic connective tissue including endothelial cells, Kupffer cells, and the blood forming
cells arise from the mesodermal cells of the septum transversum and splanchnic mesoderm.
Proliferating plates or cords of liver cells, hepatocytes, meet the vitelline veins (vv.
omphaloentericae) which course from the yolk sac to the sinus venosus of the developing
heart. They disrupt their continuity and push their endothelium, forming the network of
hepatic sinusoids. The portions of vitelline veins before the liver primordium become the
afferent veins of the liver, vv. hepaticae advehentes, and the portions of the vitelline veins
behind the liver are termed efferent hepatic veins, vv. hepaticae revehentes. Revehent
hepatic veins open into the inferior vena cava.
From the advehent hepatic veins, respective from the caudal anastomosis between the right
and left vitelline vein and the caudal segment of the right vitelline vein (see Chapter 12,
Development of venous system) vena portae develops.
Later, the hepatocyte cords become oriented in the radial fashion around the central veins.
Even later, the connective tissue becomes organised around, forming the liver lobules.
Haematopoietic stem cells establish haematopoietic islands. Mesoderm from the septum
transversum gives rise to the liver capsule and liver ligaments. The mesoderm of the septum
transversum and ventral mesogastrium between the liver and the lesser curvature of the
stomach forms the lesser omentum. The portion of the mesoderm between the liver and the
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tendinous centre of diaphragm forms the coronary and triangular ligaments and the portion
of mesoderm between the liver and the ventral abdominal wall forms the falciform ligament,
in which the left umbilical vein runs from the umbilicus to the liver.
Initially, the left and right liver lobes develop, later the right lobe forms two outgrows, the
quadrate and caudate lobes.
The liver grows quickly and expands to occupy the most of the abdominal cavity. So called
liver prominence is observable on the outside of the embryo closely behind the heart
prominence.
The caudal part of the hepatic diverticulum forms the gall bladder and cystic duct. (Fig.
13.16) Because the primordium of the gall bladder and cystic duct atrophy during early
embryological development in horses, rats and whales, a gall bladder is not formed in these
animals.
The stem of the original diverticulum between the foregut and the place where the hepatic
duct and the cystic duct join gives rise to the common bile duct, ductus choledochus.
13.13. Pancreas
The pancreas develops from dorsal and ventral endodermal buds, which arise from the
caudal portion of the foregut, more precisely at the level of foregut-midgut junction. The
larger dorsal pancreatic bud appears first and grows rapidly between the layers of the dorsal
mesentery. Later the dorsal bud develops into the right and left lobe.
The ventral pancreatic bud develops near the entry of the common bile duct and grows into
the ventral mesentery. Originally this bud is paired, but in mammals the left part early
obliterates. (Fig. 13.16)
With the first rotation of the stomach around a longitudinal axis, the ventral pancreatic bud is
moved dorsally to the right, close to the dorsal bud. During the next development these two
buds fuse to the single organ, giving rise to the pancreatic head (caput pancreatis).
Pancreatic body and tail develop from the left lobe of the dorsal bud.
In animals the final form and arrangement of the pancreas vary widely. There may be up to
three separate pancreases, which fuse in adults, but several exceptions exist. When a single
pancreas is present, only dorsal (pigs and cattle) or only ventral (sheep, goats, cats) ducts may
persist, or persist both, each draining separately into the duodenum (horses, dogs, humans).
Birds, for example, typically have three ducts. In a few other species, such as rabbits, there is
no discrete pancreas at all, and the pancreatic tissue is distributed diffusely across the
mesentery and even within other nearby organs, such as the liver or spleen.
The cells of the pancreatic buds proliferate in an arboreal fashion and give rise to the ducts
and associated secretory acini. The endodermal cells differentiate to both the exocrine acini
and endocrine islets of Langerhans. The clusters of endodermal cells gradually lose their
connection to the exocrine portion and differentiate to the glucagon, insulin and somatostatin
producing cells.
The connective tissue of the pancreas (capsule, interstitial tissue) develops from the
splanchnic mesoderm.
130
90°
16
6
9
2
6
2
1
1
8
5
7
4
3
3
17
4
14
A
B
6
5
12 8
2 9
11
1
10 4
3
C
5
6
12
11
10
1
15
5
8 9
4
2
3
D 13
131
Figure 13.16 Sequential stages in
the development of the liver and
pancreas.
1 - primordium of the stomach,
2 - primordium of the duodenum,
3 - primordium of the liver,
4 - primordium of the gall bladder,
5 - ventral pancreatic primordium,
6 - dorsal pancreatic primordium,
7 - hepatopancreatic duct,
8 - pancreatic duct,
9 - accesory pancreatic duct,
10 - hepatic duct,
11 - cystic duct,
12 - common bile duct,
13 – coronary ligament,
14 – septum transversum,
15 – diaphragm,
16 – dorsal mesogastrium,
17 – ventral mesogastrium
Modified from Sinowatz and Rűsse
(2007).
13.14. Intestine
The intestine develops from that portion of the foregut which is positioned caudal to the
developing stomach, and from the entire midgut and hindgut. Initially, the intestine
primordium is the straight tube in the longitudinal axis of the germ. Only a short portion of
the foregut has both a dorsal and ventral mesentery. Ventral mesentery of the midgut and
hindgut atrophies.
The midgut rapidly elongates forming a ventral U-shaped loop of gut – the midgut loop (also
primary intestinal loop or umbilical loop). Initially, the ventral curvature of the midgut loop
is widely connected with the yolk sac. Later this connection becomes due to body folding
narrower and subsequently obliterates as the yolk sac regresses. At the ventral apex of the
midgut loop the vestige of vitelline duct is evident. (Fig. 13. 17)
midgut
foregut
hindgut
11
2
6
9
4
5
3b
1
10
3a
8
7
3
Figure 13.17 Development of the intestine. Axially positioned primitive intestine
elongates forming a midgut loops. 1 – duodenal loop, 2 – duodeno-jejunal loop, 3 – midgut
loop, 3a – descending limb of the midgut loop, 3b – ascending limb of the midgut loop, 4 –
primordium of the stomach, 5 – primordium of the liver, 6 – primordium of the pancreas, 7 –
vitelline duct, 8 – cloaca, 9 – dorsal mesentery, 10 – ventral mesentery, 11 – aorta and cranial
mesenteric artery
132
The most caudal portion of the foregut also elongates forming ventral curvation, a primitive
duodenal loop (flexura duodenalis). From this part the cranial portion of duodenum develops.
Transitional part between the duodenal loop and the midgut loop, termed the duodenojejunal loop (flexura duodeno-jejunalis), and short proximal portion of the descendent limb
of the midgut loop develops into the caudal part of the duodenum. The rest of the descendent
limb gives rise to the jejunum. The ascendant limb of the midgut loop develops into the ileum,
the caecum, the ascending colon and the proximal portion of the transverse colon.
The midgut receives its blood supply from the branch of the dorsal aorta, the cranial
mesenteric artery, which is located in the dorsal mesentery. (Fig. 13.18)
By reason that the intestine elongates more rapidly than the space of the abdominal cavity,
which is more over partially filled by the developing liver, the intestine loops outgrow this
space and occupy part of the extra-embryonic coelom called an umbilical sac. This
herniation, which is a normal occurrence during this period of the foetal development, is
referred to as physiological umbilical herniation (hernia umbilicalis physiologica).
During the physiological umbilical herniation, the midgut loop rotates clockwise around the
dorso-ventral axis with the cranial mesenteric artery located in the axis. This first phase of
rotation accounts for 180°, so that the descending limb is displaced to the right caudally and
the ascending limb to the left cranially. The descending limb increases in length and forms a
number of coiled loops.
Later in consequence of the growth of the abdominal cavity the hernia reduces, intestine loops
return back and an additional rotation augments the rotation to about 270°. The final rotation
is species-specific, in horses or dogs the full extent of rotation is about 360°.
As the caecal diverticulum impedes the return of the ascendant limb, the descendent limb is
first to return, passing to the left, caudal to the cranial mesenteric artery, and occupying a
position medial to the hindgut and its mesentery. Thus the descending colon is pushed to the
left. The long coils of the jejunum occupy the major portion of the ventral abdominal cavity;
ileum becomes positioned to the right of the median plane. The caecum heavily enlarges and
becomes inserted between the ileum and ascending colon in the right half of the abdominal
cavity. Only in pigs the caecum is positioned to the left. The transverse colon, oral portion of
which developed from the aboral portion of the midgut and the aboral portion from the
hindgut, always becomes localized in a right to left orientation just cranial to the descending
colon, extending caudally to the left.
The most aboral portion of the hindgut gives rise to the rectum and to the allantois. The
hindgut terminates in the cloaca, differentiation of which will be described in conjunction
with the urogenital system.
The cloaca is closed caudally by the cloacal membrane. After its break anal orifice is
established. The first zone of the anal canal (canalis analis), anal zone, develops from the
endoderm; inner lining of the intermediate zone (zona intermedia) and cutaneous zone
(zona cutanea) originates from the ectoderm. Epithelial buds give rise to the anal glands of
pigs and dogs and to the circumanal glands of dogs.
The epithelium of the intestine as well the parenchyma of its derivatives, such as liver
and pancreas, are derived from the endoderm, whereas the connective tissue, muscular
components, serosal coverings and mesenteries are all derived from the mesoderm of
splanchnopleure. In the small intestine, proliferation of the mesenchyme against the base of
the epithelium forms the intestinal villi. Between them, epithelial buds leak into the
mesenchyme, undergo the luminisation and give rise to the tubular intestinal glands,
Lieberkühn´s crypts and the Brunner´s glands of the duodenum. In the large intestine,
initially the intestinal villi are established but later they longwise fuse, whereby the intestinal
133
1
3
5
6
B
A
7
2
4
7
B
C
15
16
1
15
16
8
14
13
8
13
9
12
12
10
11
11
D
1
8
1
8
E
16
16
15
9
9
12
12
13
17
11
11
Figure 13.18 Development of the intestine. Sequential stages of the gut rotation. Left
view. A – primitive intestine in axial position, primitive gut loop is connected with the yolk
sac by vitelline duct (ductus omphaloentericus), which later obliterates as the yolk sac
regresses. B – primitive gut loop prior to rotation in direction of arrow. C –clockwise rotation
of the gut loop by 180° around dorso-ventral axis. D – clockwise rotation by 270 °. E – final
134
arrangement of the limbs of the midgut in carnivores. 1 – stomach, 2 – liver, 3 – pancreas, 4 –
vitelline duct, 5 – aorta, 6 – cranial mesenteric artery, 7 – dorsal mesentery, 8 – duodenum, 9
– jejunum, 10 – vitello-intestinal duct, 11 – ileum, 12 – caecum, 13 – ascending colon, 14 –
cranial mesenteric artery, 15 – transverse colon, 16 – descending colon, 17 – mesentery.
Modified from McGeady et al. (2006).
glands extend throughout all thickness of lamina propria mucosae. Some lymphoreticular
tissue also differentiates during the embryonic development in the lamina propria mucosae in
form of solitary or aggregated nodes.
Prenatally, inside the intestine viscous and sticky like tar mass, termed meconium, forms
from the intestinal epithelial cells, mucus, amniotic fluid, bile and water, which foetus
swallows. Meconium is the earliest infant stools.
13.15. Gastrointestinal tract of birds
At about the third day of the development of the chick, four pairs of ectobranchial clefts are
observable behind the mouth. Together with four endodermal endobranchial pouches they
separate 5 pharyngeal arches.
Caudally, from the next portion of the foregut the oesophagus develops. Many birds possess a
muscular pouch along the oesophagus called a crop (ingluvies). The crop functions to both
soften food and regulation its flow through the system by storing it temporarily. The size and
shape of the crop is quite variable among the birds. Members of the order Columbiformes,
such as pigeons, produce nutritional crop milk, which is fed to their young by regurgitation.
The avian stomach arises from a simple gastric primordium, the cranial part of which
becomes the glandular proventriculus and the caudal part a proper muscular ventricle or
gizzard, composed of four muscular bands that crush and grind a food. The gizzard of some
species contains small pieces of grit or stone swallowed by the bird to aid in the grinding
process of digestion, supplying the function of mammalian or reptilian teeth.
The intense growth of the intestine loops is observable. The reminder of the vitelline duct
forms the blind prominence, diverticulum Meckeli, at the level of ileum. Birds typically have
two paired caeca, unlike mammals.
The colon heavily elongates and opens into the cloaca, which is the common passage of
digestive, urinary and genital ways. The roof of cloaca gives rise to the dorsal diverticulum,
bursa Fabricii, the site of haematopoiesis. Lymphoid stem cells migrate from the foetal liver
to the bursa during ontogeny. In the bursa, these stem cells acquire the characteristics of
mature, immunocompetent B cells. The bursa is active in young birds. It atrophies after about
six months.
The liver develops similarly like in mammals, as well as pancreas, in which both ducts persist.
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14 RESPIRATORY SYSTEM
In mammals, the respiratory system consists of a conducting portion and a respiratory portion.
The conducting portion comprises the nostrils and nasal cavities, paranasal sinuses, pharynx,
larynx, trachea, bronchi and bronchioles. The respiratory portion, which is involved in
gaseous exchange, includes the respiratory bronchioles, alveolar ducts, alveolar sacs and
alveoli.
The development of the respiratory system is closely associated with formation of the
ectodermally lined stomodeum and the endodermally lined primitive gut.
14.1. Nasal cavity
The development of the nostrils and the nasal cavity are discussed in association with the
development of the oral cavity (see Chapter 13, Primary oral and nasal cavities).
The oro-nasal membrane, separating the primary oral and nasal cavities becomes replaced
by the secondary palate, which develops by fusion of the primary palate and palate
processes, extending from the maxillary bones, except for the paired incisive ducts. (Fig.
13.4) Concurrently, the nasal septum (septum nasi) partitions common nasal cavity to the
right and left. Septum nasi grows from the dorsal aspect of the nasal cavity ventrally and fuses
with the palate processes. (Fig. 13.5) In connection with formation of the splanchnocranium
nasal cavity elongates cranio-caudally and nasal passages, which open caudally by
secondary choanae into the pharynx, are formed. (Fig. 13.2)
The rostral two-thirds of the palate processes undergo intramembranous ossification, forming
the hard palate. The nasal septum ossifies caudo-cranially.
The nasal conchae develop from the lateral aspect of the nasal cavity like the processes,
which firstly consist of the mesenchymal core covered with the ectodermal epithelium and
later undergo endochondral ossification. The conchal processes developing from the nasal
bone give rise to the dorsal and medial nasal conchae and the ventral nasal concha
develops from the conchal process of the maxilla. Conchae developed from the ethmoid bone
in the caudal region of the nasal cavity form the ethmoidal labyrinth.
Most of the ectodermal epithelium of the nasal cavity develops into the pseudostratified
epithelium with the ciliated cells and goblet cells. It is typical for the respiratory region
(regio respiratoria). In the caudo-dorsal portion of the nasal cavity in the pseudostratified
epithelium differentiate neurosensory cells, bipolar olfactory neurons and this area presents
the olfactory region (regio olfactoria). In both regions, the epithelial thickenings or buds
give rise to the nasal or olfactory glands.
As mentioned above the fusion of the palate processes and the primitive palate is incomplete
and leaves the incisive ducts as the canals between the oral and nasal cavity. A secondary
evaginations develop from the canals and extend caudally in the ventral mucosa of the nasal
cavity as the paired vomeronasal organ. The ducts of the vomeronasal organ are lined by the
ectodermal epithelium differentiating into the respiratory as well as the olfactory regions.
The paranasal sinuses develop as the solid outgrows of the ectodermal epithelium which
penetrate the bones of scull. Later a lumina develop, which open into the nasal cavity. The
final size, shape and extent of the paranasal sinuses are species specific.
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14.2. Larynx
The larynx, together with trachea, bronchi and lungs, develop from the endoderm of the
cranial portion of the foregut just caudal to the developing pharynx.
So called respiratory primordium develops as a ventral groove in the floor of the foregut at
the level of the fourth pharyngeal arch. The groove, referred to as the laryngo-tracheal
groove, deepens and forms elongated outgrowth, which extends in a caudal direction and
becomes separated from the oesophagus externally by the tracheo-oesophageal grooves.
Internally, the next deepening of the tracheo-oesophageal grooves results in their fusion and
formation of the tracheo-oesophageal septum, which separates the dorsal portion of the
foregut, the primordium of the oesophagus from the ventral portion, the primordium of the
laryngo-tracheal tube. While the epithelium of the larynx derives from the foregut
endoderm, the cartilages and muscles develop from the splanchnic mesoderm.
6
A
D
5
1
3
4
2
B
5
9
3
7
E
8
C
6
4
Figure 14.1 Sequential stages in the formation of the respiratory diverticulum from the
foregut. 1 – foregut, 2 – laryngo-tracheal groove, 3 - tracheo-oesophageal groove,
4 – respiratory diverticulum, 5 – pharynx, 6 – primordium of oesophagus, 7 – primordium of
trachea, 8 – primordia of principal bronchi, 9 – tracheo-oesophageal septum. Modified from
McGeady et al. (2006).
137
The mesoderm of the left and right fourth pharyngeal arches gives rise to two swellings which
develop lateral to the laryngo-tracheal groove, the primordia of the arytenoid, thyroid and
cricoid cartilages. These swellings compress the cranial portion of the slit-like laryngotracheal groove into a T-shaped aperture, the laryngeal glottis. A single swelling which
develops from the mesoderm of the eminentia hypobranchialis, originating from the third and
fourth pharyngeal arches cranial to the developing glottis, is named epiglottal swelling and
gives rise to the epiglottic cartilage. Caudo-laterally, the paired arytenoid swellings form
from the sixth arch. The mesenchyme of the fourth-six complex of pharyngeal arches gives
rise to the thyroid and cricoid cartilages as well as the intrinsic laryngeal muscles.
As the laryngeal cartilages develop, cranial vestibular and caudal vocal folds of the larynx
are formed, composed of mucosal and muscular tissue. Laterally, the endodermal epithelium
evaginates forming diverticula, referred as the laryngeal ventricles. These ventricles are
present in horses, pigs, dogs and humans.
I
1
II
2
III
IV
3
Figure 14.2 Development of the
larynx. 1 – copula, 2 – eminentia
hypobranchialis, 3 – epiglottal
swelling, 4 – T- shaped laryngeal
opening, 5 – arytenoid swellings
4
5
14.3. Trachea
The laryngo-tracheal tube elongates caudally and its blind end forks into two bronchial buds,
the primordia of the left and right lungs. (Fig. 14.1) The medial portion of the laryngotracheal tube from the larynx to the bifurcation gives rise to the trachea. Its wall consists of an
inner endodermal lining and an outer layer of splanchnic mesoderm. The endodermal lining of
the tube gives rise to the ciliated pseudostratified epithelium, rich in goblet cells, and
epithelial buds develop to the tracheal glands. Other components of the tracheal wall are of
the mesodermal origin and it is referred that at least in the cervical region the cells from the
ganglion crest participate on the formation of the tracheal rings.
14.4. Bronchi and lungs
The blind caudal end of the laryngo-tracheal tube forks into two bronchial buds. (Fig. 14.1E)
The smaller left bud grows in a more lateral direction then does the larger right one. (Fig.
14.3A) Each bronchial bud enlarges, forming a left and right principal bronchus. These
bronchi elongate caudally, between the developing oesophagus dorsally and the developing
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heart ventrally. In domestic animals, the right principal bronchus gives off four lobar
bronchi for the cranial, middle, accessory and caudal lobes. The middle lobe is not present in
horses. The left principal bronchus in domestic animals gives off two lobar bronchi for the
cranial and caudal lobes. In ruminants and pigs, the right cranial lobar bronchus, which is
given directly from the trachea, is referred to as the tracheal bronchus. (Fig. 14.3)
Figure 14.3 Development of the bronchial tree. 1 – trachea, 2 – tracheal bronchus, 3 – right
and left bronchial buds, 3a – principal bronchi, 4 – lobar bronchi, 5 – right cranial lobe, 6 –
middle lobe, 7 – right caudal lobe, 8 – accessory lobe, 9 – left cranial lobe, 10 – left caudal
lobe. Modified from Sinowatz and Rűsse (2007).
139
During the next development, the lobar bronchi ramify and give off segmental bronchi
which supply large portions within the lobes, so called broncho-pulmonary segments. The
number of broncho-pulmonary segments within a particular pulmonary lobe varies from
species to species. All above mentioned branches of the bronchial tree at this stage of
development are lined by the simple columnar endodermal epithelium.
The segmental bronchi undergo up to 20 bifurcations depending on the species (so called
dichotomous branching). These tubes with decreasing diameter approaching finally 0.5 mm
are referred to as terminal bronchioles. Each terminal bronchiole subdivides into two or
more respiratory bronchioles, which are structurally similar to terminal bronchioles except
that their walls give off numerous saccular alveoli where gaseous exchange takes place. These
respiratory bronchioles represent the transitional zone between the conducting and respiratory
portions of the respiratory system. The respiratory bronchioles give off a number of alveolar
ducts from which alveolar sacs and alveoli rise.
The developing bronchial tree protrudes into the common pleuro-pericardial cavity and
becomes surrounded externally by mesenchyme that forms the visceral pleura (developed
from splanchnopleure). This surrounding mesenchyme is essential for the normal lung
morphogenesis, which is based on the interaction between the endodermal epithelium and the
mesenchyme. After the experimental withdrawal of the mesenchyme the lung bud epithelium
fails to continue growing and branching.
The development of the bronchi and lungs can be divided into 5 successive periods:
 the embryonic period – this period extends from the formation of the laryngotracheal groove to the formation of the segmental bronchi. In this period the
developing lungs, which grow into the common pleuro-pericardial cavity, become
surrounded by visceral pleura.
 the pseudoglandular period – this period is named according to the gland-like
ramification that is seen in the bronchial tree. The tubules of the bronchial tree lined
by columnar endodermal epithelium ramify in the surrounding mesenchyme.
 the canalicular period – this period is characterized by the formation of the primordia
of those portions of the lungs which are included in the gaseous exchange. During this
period the lumina of the bronchi and bronchioles enlarge and the terminal bronchioles
give off a number of respiratory bronchioles. The rich peri-canalicular vascular
network is formed. Breathing is theoretically possible, but the lungs are too immature
and foetuses die.
 the saccular period – large number of terminal sacs bud off from the respiratory
bronchioles. The terminal sacs correspond with to primitive alveoli. Initially they are
lined by the cuboidal epithelium which later differentiates into two types of cells.
Thereby the air-blood barrier is established.
 the alveolar period – this is the period when final compartments for gaseous
exchange, the alveoli, are formed. The endodermal epithelium in the developing
alveoli differentiates into squamous type I alveolar cells, membranous pneumocytes
and cuboid or cone-like cells type II alveolar cells, granular pneumocytes.
Production of the pulmonary surfactant starts.
During the foetal development the lungs are filled with fluid, secreted from the developing
glands and supplemented by the aspirated amniotic fluid. The presence of the fluid is
140
considered to be an important stimulus for expansion of the alveoli. During the foetal period
the movements of those muscles which are associated with respiration are observable. They
prepare the respiratory muscles for breathing. At birth, most of the fluid in the respiratory
system is expelled through the mouth and nose. The first inspiration fills the respiratory
system with air and the remnant of liquid is absorbed by the epithelial cells.
14.5. Avian lungs
Birds have an entirely different respiratory system. Birds breathe using a respiratory system
that consists of a pair of lungs and a number of separate air sacs that take up some
considerable space in the body cavity of the bird. Most birds have nine air sacs; the anterior
air sacs (interclavicular, cervical, and anterior thoracic) and the posterior air sacs (posterior
thoracic and abdominal), which control air flow through the lungs, but do not play a direct
role in gas exchange. Birds ventilate their lungs by means of crosscurrent flow. (Fig. 14.4)
Avian lungs do not have alveoli, as mammalian lungs do, but instead contain millions of tiny
passages known as parabronchi, connected at either ends by the dorsobronchi and
ventrobronchi. Air flows from the parabronchi into air vesicles, called atria, which project
radially from the parabronchi. These atria give rise to air capillaries, where oxygen and
carbon dioxide are traded with cross-flowing blood capillaries by diffusion.
Initially the development of the avian respiratory system is similar to that of mammals. The
lungs develop from the blind end of the laryngo-tracheal tube. Two bronchial buds are
established. By the next repeated ramification the system of bronchial tree develops, including
dorsobronchi, parabronchi with air capillaries and ventrobronchi. Then the air sacs from the
lung foundation evaginate.
parabronchi
ventrobronchi
cervical
sac
dorsobronchi
interclavicular
sac
abdominal
sac
intrapulmonary bronchus
trachea
laterobronchus
syrinx
primary
bronchus
Figure 14.4. Respiratory system of birds
141
cranial
thoracic
sac
caudal
thoracic
sac
15 URINARY SYSTEM
Early development of the urinary system is closely associated with the development of the
genital system. Both develop from the intermediate mesoderm, which is also referred to as the
nephrogenic plate, and the neighbouring mesodermal coelomic epithelium. Early
proliferation of this portion of the mesoderm causes the creation of the longitudinal swelling,
termed urogenital ridge, along the dorsolateral aspect of the coelom cavity. The urogenital
ridge later divides into the mesonephric and gonadal ridges.
Some portions of the urinary system are used for the formation of some portions of the genial
system.
15.1. Kidney
Mammalian kidney develops from the intermediate mesodermal plate (nephrogenic,
urogenital plate) (Fig. 5.6) in the process of nephrogenesis.
The nephrogenic plate undergoes segmentation to individual cell groups, which create from
somites laterally emanating stems. These stems present the base of urinary system and due to
their segmentation they are termed nephrotomes. From nephrotomes pronephros and
mesonephros and metanephros develop. These kidney primordia rise in an anterior-posterior
wave of cellular differentiation. As the more caudal nephrotomes develop and become
functional, the more caudal pronephric and mesonephric nephrotomes atrophy and
metanephros persists as the definitive functioning kidney.
The evolutionary development of the kidney is illustrated by the increasing refinement of
renal structure and function evident in vertebrate animals. Lower animals, e.g. amphioxus,
have relatively primitive kidney, pronephros. In fish and amphibians, the pronephroi are
replaced by the mesonephroi and in reptiles, birds and mammals the metanephroi (definitive
kidneys) succeed the two previous structures, which atrophy.
15.1.1. Pronephros
The pronephros develops from the fourth or fifth cervical to the third thoracic nephrotomes in
early stage of embryonic development. Short evaginations, pronephric tubules grow
dorsolaterally from each nephrotome. The distal end of each tubule extends initially in a
lateral direction and then curves caudally, fusing successively with the following tubule
developing immediately caudal to it. In this way the excretory pronephric duct arises from
fusion of the distal ends of pronephric tubules. (Fig. 15.1) The pronephric duct becomes
canalised and continues to grow caudalward until it opens into the ventral part of the cloaca.
Inside each nephrotome the cells space out forming the cavity, nephrocoele. The lumen of
each pronephric tubule becomes continuous with the nephrocoele which opens into the
coelomic cavity through the aperture named a nephrostome.
Branches from the dorsal aorta form clews of capillaries, glomeruli, which may invaginate
either into the coelomic epithelium, or alternatively into the wall of each pronephric tubule.
Glomeruli which invaginate into the coelomic epithelium are referred to as external
glomeruli and those which invaginate into the tubular wall are termed internal glomeruli.
(Fig. 15.2) Formation of external glomeruli is typical for lower vertebrates. External
glomerular filtration is less efficient because the filtrate has to be propelled from the coelomic
cavity to the pronephric tubule by the ciliary action of the cells surrounding the nephrostome.
In higher vertebrates, with formation of internal glomeruli the connection between the
pronephric tubules and the coelomic cavity is lost.
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pronephric tubules
IV.c
V.c
pronephric duct
VI.c
VII.c
I.t
II.t
III.t
nephrotomes
Figure 15.1 Development of the pronephros. Fusion of pronephric tubules and formation
of the pronephric duct. c – cervical nephrotomes, t – thoracic nephrotomes
dorsal aorta
somite
nephric tube
pronephric duct
nephrostome
coelom
dorsal aorta
internal glomerule
nephric tubule
pronephric duct
external glomerulus
coelom
Figure 15.2 Development of the pronephros, later stage showing formation of the
pronephric duct and the internal and external glomerulus. Modified from McGeady et al.
(2006).
143
15.1.2. Mesonephros
The mesonephros develops from the intermediate mesoderm of the thoraco-lumbal region. In
lower vertebrates like fish and amphibians, the mesonephros is fully operational permanent
organ but in mammals its occurrence is only transitory.
Initially, original nephrotomes related to the individual somites fuse to the mesonephric mass
or mesonephric blastema, which subsequently decays to the bigger number (40–80 in
domestic animals) of cellular groups then before it. Inside each globular node the cavity,
nephrocoele is formed and entire structure (so called nephric vesicle) elongates forming the
mesonephric tubule. A series of mesonephric tubules join with laterally positioned
pronephric duct, which becomes the mesonephric or Wolffian duct. Each tubule is apposed
to a blood vessel on its medial end. The mesonephric tubules lengthen rapidly and form an Sshaped loops. (Fig. 15.3)
This proliferation, observable on the roof of coelomic cavity as a projection or column of
tissue, is referred to as urogenital ridge. Later this structure divides into a medial genital
ridge and a lateral urinary ridge.
The medial end of each mesonephric tubule invaginates and embraces the glomerular tuft
forming Bowman´s capsule. Together these structures constitute a filtration unit known as a
primitive renal corpuscle. The first portion of mesonephric tubule behind the renal corpuscle
is lined by a simple columnar epithelium with secretory function, so that is termed tubulus
secretorius, while in the next part the same type of epithelium lacks capacity of secretion and
this portion is termed tubulus collectivus. (Fig. 15.3)
With the development of the mesonephric system, pronephric tubules and the cranial portion
of the pronephric duct atrophy.
The lifetime of mesonephros is relatively short. The regression proceeds caudally and cranial
compartments degenerate. The caudal portion including Wolffian duct persists, loses the
connection with urinary system and later becomes the component of genital system.
By the former conceptions, the intermediate mesoderm segments to the nephrotomes, that
gives rise to the pronephros and mesonephros. Modern visualization methods, combined with
the simple approach of peeling off the epidermis to see the forming kidney, have shown that
nephric mesenchyme separates from the intermediate mesoderm as a single elongated
primordia. This mass sequentially decays into groups of cells, which undergo
epithelialization, forming gradually pronephric and mesonephric tubules. Each tubule is
apposed to a blood vessel on one end (future Bowman´s capsule) and connects to the
pronephric duct on the other.
15.1.3. Metanephros
The metanephros, permanent kidney in mammals, is derived from two primordial structures:
the ureteric bud, an outgrowth of the Wolffian duct, and the metanephric blastema, which
develops by the fusion of the sacral nephrotomes.
The ureteric bud is an epithelial diverticulum, which arises from the caudal portion of the
mesonephric or Wolffian duct at the level of the first sacral vertebra.
The ureteric bud extends in dorso-cranial direction and projects into the metanephric
blastema, located on the lateral aspect of the aorta. The dilated terminal portion of the ureteric
bud gives rise to the pelvis and its branches to the collecting ducts of the definitive kidney.
The manner in which the dilated end of the ureteric bud differentiates influences the final
anatomical arrangement of the kidney in mammals.
144
The formation of the collecting ducts stimulates the metanephric tissue, which surrounds each
newly formed collecting duct like a cap. It condenses in order to form peritubular cell
aggregates. Moreover, this interaction leads to a dramatic transformation of these cells into
epithelial cells. The aggregates organize into epithelial cords that canalize to form tubules.
Their terminal portions dilate and transform to the vesicles with a central lumen and a basal
lamina on its outer surface. The tubules elongate, become S-shaped and differentiate to a
proximal, middle and distal section. The epithelial cells of the vesicle, which give rise to the
glomerular capsule or Bowman´s capsule, secrete angiogenic factors. Thereby capillaries
grow into the pocket and differentiate into glomerulus. (Fig. 15. 4)
Figure 15.3 Formation of the mesonephric duct and tubule. 1 – nephric vesicle, 2 –
pronephric tubule, 3 – paramesonephric or Müllerian duct, 4 – dorsal aorta, 5 – somite, 6 coelom, 7 – developing mesonephric tubule, 8 – mesonephric or Wolffian duct, 9 – urogenital
ridge, 10 – Bowman´s capsule, 11 – lumen capsulae, 12 – glomerulus, 13 - tubulus
secretorius, 14 – tubulus collectivus
As soon as the afferent vessels come into close contact with the vesicular epithelium, it
flattens and forms a cup with a bilaminar structure, Bowman's capsule. Thus the renal
corpuscle is created.
At the same time as the formation of the renal corpuscle, the distal end of the epithelial
vesicle fuses with the neighbouring collecting duct. The metanephros thus becomes able to
145
function and can filter the plasma from the glomeruli. Through the proximal tubule the
glomerular filtrate (primary urine) gets into the intermediate tubule or Henle´s loop, the
distal tubule, connecting tubule and collecting duct. In these tubules the secondary urine arises
through resorption and secretion processes. It then reaches the renal pelvis and, via the ureter,
the bladder. During the pregnancy, the foetal urine is excreted into the amniotic cavity.
Fibrous and adipose capsules of the kidney develop from the surrounding mesenchyme.
1
4
5
6
2
A
B
3
10
12
13
8
7
8
5
5
C
9
D
11
Figure 15.4 Development of the metanephric tubule and formation of the renal
corpuscle. A – splitting of the metanephric blastema around the ureteric bud, B – parts of
metanephric blastema give rise to vesicles and small S- shaped tubules. Capillaries grow into
the blind end of tubule. C – capillaries ramify, curve and form glomerulus which becomes
surrounded by Bowman´s capsule. D – renal tubule differentiates to the proximal and distal
tubules, which are connected by the Henle´s loop. Renal corpuscle together with renal tubule
form nephron. Modified from Sinowatz and Rűsse (2007).
1 – cap of metanephric tissue, 2 – renal vesicle, 3 – ureteric bud with two ampullae, 4 – renal
tubule, 5 – collecting tubule, 6 – blood vessel, 7 – developing renal tubule, 8 – renal
corpuscle, 9 - proximal tubule, 10 – distal tubule, 11 - Henle´s loop, 12 – glomerulus, 13 –
Bowman´s capsule
146
15.1.4. Unilobar (unipyramidal) kidneys
Interspecific differences in macroscopic appearance of the mature kidney result from
differences in the branching of the ureteric bud. (Fig. 15. 5)
In developing kidney of rodents and rabbits, the renal pelvis gives off a number of branches
which project into the metanephric blastema and become the collecting ducts. Under the
inductive influence of the collecting ducts metanephric tissue forms primitive cords and
subsequently primitive tubules. One end of each tubule joins to the collecting duct and the
other, after invagination of glomerulus forms Bowman´s capsule. Finally, the tubule
elongates and differentiates to the proximal tubule, the loop of Henle and the distal tubule.
In this way a nephron, which consists of the glomerulus, the Bowman´s capsule, the
proximal and distal tubule and the loop of Henle is constituted as a basic morphologic unit of
the kidney. A renal lobule consists of a collecting duct and the associated nephrons which
drain into it. The kidney parenchyma subdivides to the cortex, where mainly the renal
corpuscles and proximal and distal tubules are located and to the medulla which is formed by
Henley loops and collecting ducts.
Due to the conical arrangement of collecting ducts, a pyramidal prominence into the renal
pelvis is formed and this structure is referred to as medullary pyramid. The apex of the
pyramid protruding into the cup-like pelvis is named papilla. The medullary pyramid with its
associated portion of the cortex constitutes a renal lobe. Because the kidneys of rodents and
rabbits have a single pyramid, they are referred to as unilobar kidneys.
15.1.5. Multilobar (multipyramidal) kidneys
In cattle, the ureteric bud forms two major branches (primary branches), that subdivide into
15 to 25 minor (secondary) branches. Consequently 15 – 25 separate lobes, each with its
distinct pyramid (papilla) develop. The papillary ducts within each lobe drain into a calyx.
In the pig, although the cortex is not lobated and the kidney surface is smooth, the medulla is
subdivided into the renal pyramids forming papillae. The porcine kidney is multipyramidal.
The dilated end of the ureteric bud forms renal pelvis, which is subdivided into two major
divisions, major calyces, from which up to ten funnel-shaped minor calyces originate.
In the horse, small ruminants and carnivores no calyces are formed and the papillary duct
drains directly into the common pelvis. In the horse, the renal pelvis evaginates to thin-walled
processes, terminal recesses, which are lined with the same epithelium as the collecting ducts
and may be regarded as fusions of collecting ducts originating from the nephrons located near
the poles of kidney. The cortex undergoes a complete fusion resulting in a non-lobated,
smooth surface. Moreover, fusion of the apical regions of the medullary pyramids results in
the formation of a ridge-like common papilla, the renal crest. In carnivores, complete fusion
of the cortical areas of adjacent lobes imparts the superficial appearance of a unilobar kidney.
The ridge-like papilla, the renal crest develops by the fusion of apices of medullary pyramids.
The fusion of the pyramidal apices conveys the impression that kidneys of carnivores are
unilobar. However, the multilobar structure is confirmed by the presence of cortical columns
and the position of the interlobar arteries, which delineate individual lobes. Typical feature of
the kidneys of domestic carnivores is the presence of deep lateral recesses of the renal pelvis,
which segregate the medullary regions into wedge-shaped structures called renal pyramids.
The kidneys of sheep and goats develop in a manner comparable to those of domestic
carnivores.
In aquatic mammals including seals, otters and whales and in bear the terminal end of the
ureteric bud gives rise to a number of branches each capped by metanephric tissue forming a
147
kidney lobe, termed renculus. Each individual lobe is formed in a manner similar to that
described for a unilobar kidney. The multilobar kidney in these species resembles a bunch of
grapes, with individual lobes draining separately into a branch of the ureter.
A
B
C
D
E
Figure 15.5 Development of the renal pelvis, calyces and collecting tubules of the
metanephros. A – branching of dilated end of the ureteric bud in the metanephrogenic
blastema, B – differentiation of the ureteric bud in carnivores, pig (C), bovine (D) and horse
(E)
148
15.2. Urinary bladder
The urinary bladder originates mainly from the cloaca and minutely the ductus allantoideus
participates on its development. During development of the hindgut, the cloaca is subdivided
by the urorectal septum into the rectum dorsally and the primitive urogenital sinus
ventrally. Cranially, the urogenital sinus is connected to the allantoic cavity through the
ductus allantoideus. At the point of entry of the mesonephric or Wolffian ducts, the primitive
urogenital sinus divides into the cranial vesico-urethral base and the caudal urogenital sinus
proper. As the urinary bladder grows, its expanding wall incorporates the terminal portions of
the mesonephric ducts and the ureteric buds and each duct system develops its own separate
openings into the developing bladder. Initially, the mesonephric ducts open anterior to the
ureteric buds, but gradually the positions of these orifices shift, so that the ends of ureteric
buds finally open into the bladder laterally and anterior to the mesonephric ducts. The region
of mesonephric ducts and ureteric buds incorporation gives rise to the trigone (trigonum
vesicae) in the dorsal wall of the bladder and the cranial urethra. The base of the trigone is
delineated anteriorly by the entrance of the forming ureters and the apex is located, where the
mesonephric ducts enter. (Fig.15.6)
The reminder of the vesico-urethral portion forms the body of the bladder and the first part of
pelvic urethra. The apex of the urinary bladder prolongs into the umbilicus as a narrow canal
(original ductus allantoideus), which later obliterates and forms urachus. The attenuated
distal end of the urachus changes into the solid, cord-like structure, the median umbilical
ligament, which connects the urinary bladder with umbilicus.
The trigone is lined by the epithelium of mesodermal origin, whereas the rest of the bladder
epithelium derives from the endoderm.
The non-epithelial components of the wall, connective tissue and smooth muscle, are derived
from the visceral mesoderm.
In the female, the vesico-urethral base gives rise to all the length of urethra and from the
urogenital sinus the vestibule of the vagina (vestibulum vaginae) develops. In the male, the
caudal urogenital sinus gives rise to remaining two thirds of pelvic urethra.
Figure 15.6 Formation of the urinary bladder from the ventral portion of the cloaca and
ductus allantoideus. 1 - mesonephros, 2 - Wolffian duct, 3 – ureteric bud, 3a – ureter, 4 –
Müllerian duct, 5 – rectum, 6 – septum urorectale, 7 – vesico-urethral base, 7a – primary
urethra, 8 – cloaca, 9 – urinary bladder, 10 – phallus, 11 – ductus allantoideus
149
2
2
3
3´
1
1
A
B
3´
1
1
2
3´
4
2
C
D
5
Figure 15. 7 Development of the urinary bladder. Dorsal view. Relation of the ureters and
mesonephric (Wolffian) ducts during the development. 1 – urinary bladder, 2 – mesonephric
duct, 3 – ureteric bud, 3´ - ureter, 4 – trigone of the bladder (trigonum vesicae), 5 - urethra
Modified from Sinowatz and Rűsse (2007).
150
16 REPRODUCTIVE SYSTEM
16.1. Development of the male and female genital organs
The sex of an embryo is determined chromosomally. Y chromosome is responsible for
formation of male sex; the testis-determining gene (Sry gene) is located on the short arm of
the Y chromosome.
Initially, in early period of development, the primordia of both male and female genital organs
are present. It is named an undifferentiated stage. Depending on the genetically determined
sex of the individual, the appropriate genital organs develop while genital organs for the other
sex regress.
16.1.1. Undifferentiated stage
The basic structure in the genital organs development is bilateral urogenital ridge (plica
urogenitalis), which is derived from the intermediate mesoderm along the dorsolateral aspect
of the coelom cavity.
The urogenital ridge later divides into the lateral mesonephric and medial gonadal or genital
ridges (plica mesonephridica and plica genitalis) separated by the longitudinal groove. (Fig.
16.1)
The gonadal ridge consists of the coelomic epithelium of the somatopleura and underlying
mesenchyme and extends from the thoracic to the lumbar region.
The epithelium covering the surface of the gonadal ridge is termed germinal epithelium
because it contains, except epithelial cells, relatively big, globous primordial germ cells.
These primordial germ cells can be detected in epiblast (the outer layer of a blastula that gives
rise to the ectoderm after gastrulation) by specific staining methods at an early stage in
embryonic development. Then they migrate through the primitive streak and the splanchnic
mesoderm to the yolk sac and allantois and subsequently move along the wall of the hindgut
to the genital ridge. In mammals, primordial germ cells arrive at their site of differentiation by
active migration, whereas in avian species they reach the genital ridge via the blood stream.
However, currently it is proposed, that mesonephric cells from the degenerating mesonephric
tubules contribute to the germinal epithelium development.
Originally simple cuboid germinal epithelium of the gonadal ridge becomes stratified and
starts to penetrate in form of cellular cords into the underlying mesenchyme. Primordial
germ cells divide mitotically during its migration and proliferation of cords. Only germ cells
which reach the undifferentiated gonad, developing from the lumbar region of gonadal ridge,
differentiate and survive. Most germ cells outside the gonadal region undergo apoptosis.
Sometimes, that cells which survive outside the gonadal region may form germ cell tumours
referred to as teratomata.
In connection with the formation and proliferation of cellular cords the gonadal primordium
enlarges and partially separates from the genital ridge remaining suspended on the duplicature
of somatopleura – mesogenitale.
151
1
3
2
4
4
5
6
7
7
8
9
10
11
12
13
14
15
16
17
Figure 16.1 – Development of the male and female genital system in relation to the
development of the urinary system. 1 - ductus mesonephricus, 2 – appendix testis, 3 –
ostium abdominale tubae, 4 – mesonephric tubules, 5 – paramesonephric duct, 6 – oviductus,
7 – gonadal ridge, 8 – caput epididymis, 9 – epoophoron, 10 – testes, 11 – ovarium, 12 –
paradidymis, 13 – ductus deferens, 14 – uterus, 15 – vesica seminalis, 16 – vagina, 17 –
ductus ejaculatorius. Modified from Horký et al. (1984).
152
16.1.2. Differentiated stage – differentiation and maturation of testes
In genotypic males, the cellular cords with primordial germ cells leak into the underlying
mesenchyme to form testicular or medullary cords. They elongate, distort and anastomose
and their extremities join with mesonephric tubules, which are not destroyed within this area
(epigenitale). The mesonephric tubules give rise to the efferent testicular tubules (ductuli
efferentes testis). (Fig. 16.2)
Initially, the testicular cords, known as seminiferous cords are solid structures, which are
composed from the indifferent cells on the periphery and the core formed by primordial
germinal cells or pre-spermatogonia. Later, indifferent cells differentiate into the Sertoli
cells of germinal epithelium and some of them give rise to the myoid cells, a layer of which
surrounds the cords. Under the influence of seminiferous cords, mesodermal cells, located
between the cords, differentiate into the interstitial cells (Leydig cells), which produce
testosterone.
The terminal segments of cellular cords become straighten and anastomose to each other,
forming tubuli recti and rete testis at the centre of the developing gonad.
Mesenchymal cells under the coelomic epithelium of the developing testis develop into a
fibrous layer known as the tunica albuginea and the mesenchymal cells between adjacent
cords give rise to the mediastinum, connective tissue septa and interstitial tissue of the
testicular lobes.
Through the secretion of inhibitory factors, the Sertoli cells, which surround the prespermatogonia, prevent further differentiation of the germ cells until the puberty. During the
puberty the seminiferous cords become canalised and form the seminiferous tubules (tubuli
seminiferi contorti) and spermatogenesis begins.
16.1.2.1. Descent of the testes
In most mammals, including all our domestic animals, the testes developing in a
retroperitoneal position, migrate from their site of development into the scrotum. This extraabdominal position ensures a temperature of 2 – 4 ºC below the core body temperature, which
is in these animal species required for normal spermatogenesis. In, for instance, aquatic
mammals, elephants and other vertebrate animals the testes remain within the abdominal
cavity.
Before their descent, the testes are anchored cranially by a suspensory ligament derived from
the diaphragmatic ligament of the mesonephros (cranial portion of the genital ridge) and
caudally by the inguinal ligament of the mesonephros, which later becomes the
gubernaculum testis. (Fig. 16.3) As the mesonephros degenerates, the ligaments supporting
the gonads and ducts remain attached to the wall of the peritoneal cavity. The site of
attachment shifts from dorsolateral to ventrolateral position as the ducts pass caudally. During
the first phase of descent, under the influence of androgens, the anterior suspensory ligament
regresses and testis is released from its site of development. In consequence of it the testes
fall down (so called transabdominal descent) towards the inner opening of the inguinal
canal. The third phase, during which testes moves into the scrotum, is named transinguinal
descent. This phase is androgen dependent. Meanwhile it is unknown, weather the
gubernaculum actively pulls the testis into the scrotum or just acts as a guiding structure, but
there are no contractile fibers present in the gubernaculum. As the testis approaches the
inguinal ring, the tail of the epididymis enters the inguinal canal. The gubernaculum swells,
primarily due to an increase in intercellular fluid, dilates the opening into the inguinal canal
and thereby facilitates entry of the testis. A crescentic evagination of the peritoneum, named
processus vaginalis, is pulled down into the inguinal canal. During the descent it almost
153
completely surrounds the gubernaculum, forming the visceral and parietal layers of the tunica
vaginalis. Once the testis has entered the inguinal canal, contraction of the internal opening
together with contractions of the abdominal muscles forces the testis along the canal and
through the external inguinal opening. As the testis leaves the inguinal canal, the
gubernaculum testis regresses.
The failure of testicular descent is named cryptorchidism.
4
4
8
5
3
A
6
1
B
7
3
2
13
7´
5
C
12
11
6
10
3´
9
Figure 16.2 Development of spermatic cords. 1 – proliferating coelomic epithelium,
2 – primordial germ cells, 3 – testicular cords, 3´ - seminiferous tubules, 4 – aorta, 5 –
Wolffian duct, 6 - Müllerian duct, 7 – rete testis cords, 7´ - rete testis, 8 – degenerating
mesonephric tubule, 9 – tunica albuginea, 10 – developing testicular septa, 11 – interstitial
tissue, 12 – coelomic epithelium (somatopleura), 13 – efferent ductules
154
Figure 16.3 Descent of the testis in cattle. A – The testes located extra-peritoneally on the
roof of the abdominal cavity. B – Transabdominal descent, testes move down towards the
inner opening of the inguinal canal. C – Transinguinal descent into the scrotum. 1 – testis,
2 – gubernaculum testis, 2´ - ligamentum testis proprium, 2´´ - ligamentum inguinale testis,
3 – epigenitale, 4 – Wolffian duct, 4´- caput epididymis, 4´´ - ductus deferens, 5 – vesicular
gland, 6 – prostate, 7 – bulbourethral gland, 8 – urachus, 9 – urinary bladder, 10 - urethra
155
16.1.3. Differentiated stage – differentiation and maturation of ovaries
In female animals, the absence of Sry gene and expression of Dax-1 gene suppresses the
formation of testes and allows the indifferent gonad to develop into ovaries. The sex cords
derived from the coelomic epithelium leak into the mesenchyme and grow towards the
mesogenitale, future mesovarium, where probably join with mesonephric tubules. These
primary cords, so called medullary cords, contain some primitive germinal cells, but usually
remain less well developed and subsequently decay. Due to the breakdown of medullary and
mesonephric tubules, in a less dense central area of the ovary primordium, the reminder of
these tubules, rete ovarii, may be observable. (Fig. 16.4)
Next set of sex cords, named cortical cords, reaches only the cortical region of the future
ovary. After following breakdown of cortical cords, germ cells undergo a period of enhanced
mitotic activity, which ceases before or shortly after birth. In this period of multiplication
hundreds of thousands of primordial germinal cells, oogonia are obtained, but high
percentage of oogonia later undergo degenerative change - atresia.
As the period of the mitotic activity is completed, individual oogonia become surrounded by a
layer of squamous cells, termed follicular cells. The origin of follicular cells is still disputed.
They are considered to originate from (1) the coelomic epithelium, (2) mesonephric origin or
(3) a combination of both. One oogonia surrounded by follicular cells constitutes a
primordial follicle. (Fig. 16.4) The follicular cells induce the enclosed oogonia to enter the
prophase of first meiotic division, which results in the formation of a primary oocyte. This
phase of germ cells development is named period of growth. The primary oocytes do not
progress to the tertiary stage of development, period of maturation, until stimulated by
gonadotrophic hormones at the onset of puberty.
By the end of the period of growth in domestic animals, except horses, the ovary consists of
peripheral cortical area which contains the primordial follicles, and central medullary area
composed of degenerating intra-gonadal tubules, the rete ovarii. The superficial germinal
epithelium of the ovary doesn´t revert to mesothelium, thus the ovary is not covered with the
peritoneum in the adult. The connective tissue of the ovary develops from the mesenchyme.
Closely bellow the germinal epithelium becomes denser, forming fibrous web – tunica
albuginea.
Development of follicles in equine ovary is concentrated in the central area corresponding to
the medulla of other species, while non-follicular area is located peripherally. During the next
development the surface of ovary becomes concave and coelomic epithelium is retained only
in this site. Therefore, in the mare, ovulation occurs only within the range of this concavity,
which is called the ovulation fossa (fossa ovulationis).
16.1.3.1. Descent of the ovaries
Just as in the male, there is a gubernaculum (develops from the caudal portion of plica
genitalis), which effects a distinct change in the position of the ovary, varying with species.
In cattle and pigs, the descent is pronounced, ovaries descent caudally and finally occupy the
position near the uterine horns. In the mare ovaries become positioned midway between the
kidneys and the pelvic inlet. In dogs and cats the descent is not very pronounced and ovaries
finally occupy the position in the sublumbar region caudal to the kidney. The final position of
the ovaries is stabilized by ligaments, which are remnants of cranial and caudal portions of the
genital ridge and of structures associated with the mesonephros. Cranially, the remnant of
genital ridge gives rise to the suspensory ligament of the ovary. The caudal part of the
gubernaculum between the ovary and the tip of uterus ultimately becomes the proper ovarian
156
ligament, while the part between the uterus and the labium majus forms the round ligament of
the uterus.
Figure 16.4 Differentiation of the ovary showing the formation of primordial follicles.
1 – gut, 2 – primordial germ cells, 3 – degenerating mesonephric tubules, 4 – Müllerian duct,
5 – medullary cords, 6 – rete ovarii, 7 – follicular cells, 8 – oogonia, 9 – primordial follicle,
10 – cortical cords
157
16.2. Development of the sexual duct system
16.2.1. Undifferentiated stage
The undifferentiated sexual duct system consists of paired mesonephric ducts (Wolffian
ducts) and paired paramesonephric ducts (Müllerian ducts). (Fig. 16.1) The development of
the mesonephric, Wolffian ducts has been described in connection with the development of
mesonephros. The paramesonephric, Müllerian ducts form bilaterally in both male and
female embryos on the lateral side of the mesonephros, close to the mesonephric duct.
Initially, a longitudinal paramesonephric invagination develops in the coelomic epithelium of
the mesonephric ridge. After it, coelomic epithelium invaginates into the underlying
mesenchyme forming a longitudinal groove. Margins of this groove attach and grow together.
The duct separates from the peritoneal lining. Cranial end of the duct forms a funnel, which
opens into the body cavity. The proper duct is located laterally and in parallel way with
Wolffian duct. Its caudal end elongates caudally and then turns medially. Whereby crosses
ventrally Wolffian duct, approaches to the opposite one and both open into the posterior wall
of the urogenital sinus at the Müllerian prominence.
The next fate of the indifferent genital ducts depends on the sex.
16.2.2. Differentiated stage – male sexual duct system
The development of the male genital duct system depends on hormones from the testes. AntiMüllerian hormone (AMH), also known as Müllerian inhibiting substance (MIS),
produced by the embryonic Sertoli cells, supresses the development of the Müllerian ducts,
leaving only remnants of their anterior and posterior ends - appendix testis and utriculus
prostaticus (utriculus masculinus).
As mesonephros regresses, some mesonephric tubules in the vicinity of the testes, so called
epigenitale, get connected to the cords of the rete testis, forming efferent testicular ductules
(ductuli efferentes testis). The mesonephric tubules along the posterior pole of the testis
(paragenital tubules) which do not join the rete testis are collectively called paradidymis.
Under the influence of testosterone and its metabolite, 5α-dihydrotestosterone, the next
portions of sexual ducts develop. Immediately bellow the entrance of the efferent ductules, the
mesonephric duct becomes highly convoluted, forming the ductus epididymis and ductus
deferens. Within the range of distal portion, ductus deferens, the mesonephric duct becomes
invested by a thick layer if smooth muscle cells. The most distal region of ductus deferens
posterior to the primordium of the seminal vesicle becomes the ejaculatory duct. The blind
anterior end of the mesonephric duct persists as appendix epididymis.
The male accessory sex glands development is closely associated with the formation of male
genital duct system. Most of domestic animals (boar, stallion, bull, ram) and laboratory
animals have seminal vesicles, bulbourethral gland and prostate gland. The cat lacks
seminal vesicles and in the dog only a prostate gland is found. The male accessory glands
develop as epithelial buds evaginating into underlying mesenchyme from the epithelium of
the mesonephric duct (vesicula seminalis) and the sinus urogenitalis (prostate and
bulbourethral gland). Their formation is controlled by androgens and is based on the
epithelio-mesenchymal interaction, which stimulates the surrounding mesenchymal cells to
produce growth factors. The developing glandular epithelium also induces some
mesenchymal cells to differentiate into the smooth muscle cells.
158
16.2.3. Differentiated stage – female sexual duct system
The absence of anti-Müllerian hormone enables the Müllerian ducts to develop into the
female reproductive tract, which comprises the oviductus (Fallopian tube), uterus, cervix
and vagina.
The mesonephric ducts become extinct, but occasionally a vestigial structure occurs as a small
duct lying parallel to the uterine tube, extending from the epoophoron through the broad
ligament to the vagina. This vestigial structure, named Gartner´s duct or canal may form a
cyst in the vaginal wall. Epoophoron is the vestige of the mesonephric tubules localised near
the developing ovary. The mesonephric tubules caudal to the developing gonad become
paroophoron.
The anterior parts of Müllerian ducts open into the coelomic cavity by the extended funnel,
which develops into the infundibulum of oviductus. Towards their posterior ends, the
Müllerian ducts turn medially and their transverse portions cross mesonephric ducts ventrally.
From them ampulla, isthmus and pars uterina of oviductus develop. The epithelial lining of
the oviductus rises from the coelomic epithelium of the mesonephric ridge. The next layers of
the wall have the mesenchymal origin.
After Müllerian ducts reach the midline, their posterior ends fuse, giving rise to uterovaginal
canal (canalis uterovaginalis), from which the uterus and vagina develop. The uterovaginal
canal will grow toward the urogenital sinus to contact its posterior wall. At the point of
contact, the uterovaginal canal protruding into the urogenital sinus is called the Müllerian
tubercle.
After fusion of the paramesonephric ducts in the midline, a broad traverse pelvic fold is
established. This fold, which extends from the lateral sides of the fused ducts toward the wall
of the pelvis, is the broad ligament of the uterus.
In mammals, the morphology of the uterus varies considerably depending on the extent of
fusion between the two paramesonephric ducts. (Fig. 16.5) The four main forms in which it is
found are:
Uterus duplex - there are two fully separated uteri and both cervices open separately into the
common vagina Found in marsupials, rodents and lagomorphs (rabbits and hares).
Uterus simplex - in contrast to previous the entire uterus is fused to a single organ, thus the
oviducts open into one common cavity. Typical for higher primates, including the human.
In domestic animals the posterior ends of the paramesonephric ducts fuse in varying extents.
Uterus bipartitus – the cranial portions of the uterus remain separate, giving rise to cornua
uteri separated by an intercornual septum. The caudal potions fuse, forming the uterine body,
which remains divided into two cavities by the partition, but enters the vagina by a single
cervix. Found in carnivores and pigs.
Uterus bicornis - the horns are distinct for less than half their length; the lower part of the
uterus is a common chamber, the body. The bicornuate uterus is typical of many ungulate.
The formation of uterine glands includes the level of epithelial invaginations, epithelial buds
formation, branching, elongation and coiling. The timing of uterine gland formation is highly
species-specific. In some animal species the formation of buds starts several days after birth,
like in rodents, in ungulates it starts right after birth and is completed within 12 to 56 days and
in primates, including humans it begins in utero, continues after birth and reaches its
histological maturity in puberty.
159
Figure 16.5 Types of the uterus in mammals. A – uterus duplex, B – uterus simplex,
C – uterus bicornis, D – uterus bipartitus
160
The vagina rises from fused posterior ends of the Müllerian ducts. At the point where they
join the urogenital sinus, the blind ends of Müllerian ducts fuse with the lining of the
urogenital sinus to form the epithelial vaginal plate. Subsequently, cannulation of these fused
structures occurs, forming the lumen of the vagina. Initially the lumen is separated from the
urogenital sinus by a thin membrane, the hymen, which consists of the epithelial lining of the
sinus and a thin layer of vaginal cells. In animals, the hymen subsequently breaks down, the
remnants persist only rarely. The caudal portion of the urogenital sinus forms the vestibulum
vaginae. (Fig. 16.6)
Figure 16.6 Sequential stages in the development of the vagina. Modified from McGeady
et al. (2006).
161
16.3. Development of the external genitalia
16.3.1. Undifferentiated stage
During undifferentiated stage of sexual development mesenchymal cells derived from the
primitive streak migrate to the region around the cloacal membrane and form elevated
lateral anal folds dorsally and cloacal or urogenital folds ventrally. At the cranioventral end
of the cloacal membrane the urogenital folds fuse, forming individual elevation, genital
tubercle. Later, as a consequence of the formation of the urorectal septum, the perineum is
created and the cloacal membrane is subdivided to the anal and urogenital membrane. (Fig.
9.7) Both membranes subsequently break down allowing the communication between the
rectum and urogenital sinus, and the exterior. Laterally to the urogenital folds and
caudolateral to the cloacal membrane the mesenchyme proliferates to form the labioscrotal or
genital swellings.
Shortly after the appearance of the genital tubercle the epithelial lining of the floor of the
urogenital sinus proliferates and grows into the mesoderm of the genital tubercle. These
epithelial cells form the solid cord, so called urethral plate, which extends inward from the
ventral surface of the tubercle. Endodermal cells of the urethral plate attach to the ectodermal
cells of urogenital membrane. After the rupture of urogenital membrane, the urethral plate
longitudinally invaginates to form the urethral groove, which is laterally surrounded by the
urogenital folds. (Fig. 16.7)
Figure 16.7 Undifferentiated
stage in the development of
external genitalia.
1 – tail tubercle
2 – anal fold
3 – anal orifice
4 – urogenital fold
5 – urogenital membrane
(horizontally hatched)
overlaping uretral plate (gray
under that)
6 – uretral groove
7 – genital tubercle
8 – labioscrotal swelling
162
16.3.2. Differentiated stage - formation of male external genital organs
In the male embryo, the development of the external genitalia is controlled by androgens from
the foetal testis. The genital tubercle elongates rapidly in a ventro-cranial direction and
draws the urogenital folds forwards. The urogenital folds form lateral edges of the urethral
plate, the floor of which invaginates to form the urethral groove; they proliferate and fuse in
midline, converting the groove into a tube, the penile urethra. (Fig. 16.8) With closure the
penile urethra becomes incorporated into the body of the penis. The urethral plate, however,
does not extend to the tip of the penis. An ectodermal bud which invaginates at the tip of the
penis fuses with endodermal cells lining the penile urethra. Later this bud elongates and
becomes canalised and its lumen fuses with the lumen of urethra, so that the penile urethra
opens at the tip of the penis. (Fig. 16.9) The corpus cavernosum penis, corpus spongiosum
urethrae and tunica albuginea derive from the mesenchyme of the genital tubercle, as well as
the glans penis, which develops from the apex of the genital tubercle. Later the glans penis
separates from the ectodermal outer lining so that circular plate of ectodermal cells
invaginates into the mesenchyme of the tubercle and delaminates, giving rise to a cleft, the
preputial cavity. (Fig. 16.9)
The genital (labioscrotal) swellings give rise to the scrotal pouches, which fuse in their
medial aspects forming the scrotum. (Fig. 16.8) The line of fusion of the scrotal pouches
persists as the scrotal raphe. The final position of the scrotum differs in the animal species.
In dogs, horses and cattle the scrotal pouches shift anteriorly and the scrotum is located in the
inguinal region, closely apposed to the genital tubercle. In cats and pigs the swellings remain
positioned beneath the anus.
Figure 16.8 Development of the male external sex organs. A - Closure of the urethral
groove and conversion of the urethral groove into a tube, the penile urethra. B - Fusion of
scrotal pouches gives rise to the scrotum. 1 – tail tubercle, 2 – anal fold, 3 – perineum, 4 –
scrotal pouch, 5 – labioscrotal swelling, 6 – urogenital fold, 7 – urethral groove, 8 – urethral
plate, 9 – glans penis
163
Figure 16.9 Development of the terminal portion of the penile urethra. 1 – ectoderm, 2 –
glans penis, 3 – endoderm, 4 – penile urethra, 5 – body of penis, 6 – ectodermal bud, 7 –
circular ectodermal ingrowth, 8 - prepuce
16.3.3. Differentiated stage - formation of female external genital organs
In the female embryo, the vestibule of vagina develops from the caudal part of the urogenital
sinus. (Fig. 16.6) The endodermal epithelial buds protruding into the mesenchyme give rise to
the major and minor vestibular glands. The urogenital folds, which do not fuse, develop into
the labia of the vulva. (Fig. 16.10) The genital tubercle, localised at the floor of the vestibule,
gives rise to the clitoris, which is covered by the labia at the point where these structures meet
ventrally.
Figure 16.10 Development of
the female external sex organs.
1 – tail tubercle
2 – anal fold
3 – perineum
4 – labium developing from the
urogenital fold
5 – vestibulum vaginae
6 – vaginal orifice
7 – external urethral orifice
8 – clitoris
9 – ventral commissure
10 - vulva
164
16.4. Urogenital system of birds
In birds, the pronephric and mesonephric nephrotomes atrophy and metanephros persists as
the definitive functioning kidney. The mesonephric or Wolffian ducts give rise to the
ureteric buds which grow towards the metanephric blastema and ramify to form the ureter,
pelvis renalis and complex of collecting ducts. Wolffian ducts persist, lose the connection
with urinary system and later become the component of genital system, from which ductus
epididymis and ductus deferens develop. The efferent testicular ductules (ductuli efferentes
testis) develop from the mesonephric tubules.
The Müllerian ducts develop as invaginations of coelomic epithelium near the cranial end of
the Wolffian duct. Firstly they are solid, later these cords canalize and extend caudally. In
male, Müllerian ducts remain blind and atrophy, while in female they develop to the
Fallopian tubes, which open into the cloaca. Subsequently, the left oviduct fully develops
into the infundibulum, magnum, isthmus, uterus or shell gland and vagina whereas the
right one, as well as the right ovary, decays. (Fig. 16.11)
The testes in birds remain in the abdominal cavity suspended at the duplicature of the
peritoneum.
A bird penis is different in structure from mammal penises, being an erectile expansion of the
cloacal wall and being erected by lymph, not blood. A number of duck species and ostriches
have penises but most birds do not have a penis. They mate simply by pressing their cloacas
together which is known as a “cloacal kiss“.
Figure 16.11 Urogenital system of birds. Left side – female, right side – male.
165
Male birds have paired abdominal testes lying cranioventral to the first kidney lobe. Testes
increase dramatically in size during the breeding season. The ductus deferens emerges
medially and passes caudally to the cloaca where it has a common opening with the ureter to
the urodeum. The terminal vas deferens is swollen as a storage organ, the seminal vesicle.
In most female birds, only the left ovary and oviduct persist. Active ovaries with numerous
developing follicles resemble bunches of tiny grapes. The oviduct opens medially to it in a
funnel-shaped ostium. Ovulation results in the release of an egg from a mature follicle on the
surface of the ovary. The egg, with extensive food reserves in the form of concentric layers of
yolk, is picked up by the ostium and ciliary currents carry it into the magnum region. Over
about three hours the egg receives a coating of albumen.
The egg then passes into the isthmus, where the shell membranes are deposited. This takes
about one hour. The egg then moves to the uterus, or shell gland, where the calcareous shell
is added and, in some birds, pigment is added in characteristic patterns. The egg then passes
into the vagina and cloaca for laying.
166
17 ENDOCRINE SYSTEM
The endocrine system consists of special secretory cells producing hormones directly into the
blood. These specialised secretory cells may form individual endocrine organs, the endocrine
glands, or they may occur as organised clusters within organs which do not have
exclusively endocrine function. In addition, the endocrine cells may be present as solitary
cells distributed in many tissues throughout the body.
Endocrine secretions play an important role in regulating and coordinating the normal
physiological activities of the body. The functioning of some endocrine glands may be
controlled by stimulating or inhibitory hormones produced by other endocrine glands.
The defined endocrine glands include the pituitary gland, the pineal gland, the adrenal glands,
the thyroid gland and the parathyroid glands. Organs which contain groups of endocrine cells
include the pancreas, the testes and ovaries and the placenta in pregnant females. Cells of
diffuse endocrine system are found in gastrointestinal tract epithelium, the conducting airways
of the respiratory system, the juxtaglomerular apparatus of the kidney, atrial myocardium, and
hepatic tissue.
17.1. Pituitary gland
The hypophysis (pituitary gland) develops from two quite separate parts:
1) The ectodermal evagination from the roof of the stomodeum in the midline, immediately
rostral to the oro-pharyngeal membrane, known as the Rathke’s pouch gives rise to the
adenohypophysis.
2) The ventral downgrowth in the floor of the diencephalon, the infundibulum, forms the
neurohypophysis.
The two primordial structures meet and fuse forming the pituitary gland.
The adenohypophyseal pouch (Rathke’s pouch, sacculus hypophysealis) grows
caudodorsally towards the infundibulum and subsequently loses its connection with the oral
ectoderm forming the adenohypophyseal vesicle. Cells of the rostral wall of the vesicle
proliferate in higher rate than the cells of the caudal wall. Proliferating cells from the dorsal
aspect of the rostral wall surround the stalk of the infundibulum, forming the pars tuberalis.
The remaining cells of the rostral wall proliferate forming aggregations of cell which give rise
to pars distalis. The caudal wall of the adenohypophyseal vesicle which undergoes little
proliferation comes in direct contact with the infundibulum and forms the pars intermedia.
The infundibulum gives rise to the hypophyseal stalk and an enlarged distal area, the pars
nervosa of pituitary. (Fig. 17.1)
Because of limited proliferation of the pars distalis in ruminants, pigs and carnivores, the
adenohypophyseal cleft persists, unlike horses, where the proliferation of the pars distalis
obliterates the adenohypophyseal cleft. In horses, pigs and carnivores the pars intermedia
encloses the infundibulum so that the pars intermedia is in direct contact with the surface of
the pars nervosa. (Fig. 17.2)
Cells of the adenohypophysis differentiate into endocrine cells, which based on their staining
characteristics, can be classified as acidophils, basophils and chromophobes. The
functioning of cells of the adenohypophysis is under the control of hypothalamic
neurohormones which stimulate or inhibit their secretion.
Cells of the neurohypophysis are modified astrocytes which are referred to as pituicytes.
Hormones released in the neurohypophysis are neurosecretions from the supraoptic and
paraventricular hypothalamic nuclei which are transported along axons to the pars nervosa
where they are stored. Release of them is influenced by feedback mechanism from the target
organs.
167
A
developing
brain
notochord
adenohypophyseal
primordium
oropharyngeal
membrane
infundibulum
infundibulum
adenohypophyseal
pouch
adeno
hypophyseal
vesicle
notochord
oro-pharyngeal
membrane
B
C
notochord
third ventricle
pars
tuberalis
pars
intermedia
pars distalis
infundibulum
optic chiasma
adeno
hypophyseal cleft
pars
tuberalis
pars
nervosa
pars
nervosa
oral cavity
pars
distalis
D
cartilaginous primordium of
sphenoid bone
sphenoid
bone
pars
intermedia
Figure 17.1 Sequential stages in the development of the pituitary gland.
A – the arrows indicate growth of the hypophyseal primordia, B, C - development of the
adenohypophyseal pouch and infundibulum, D – the connection of the adenohypophyseal
pouch with the ectoderm of the oral cavity becomes extinct, E – final arrangement of the
adenohypophysis and neurohypophysis. Modified from McGeady et al. (2006).
168
E
Figure 17.2 The relationships of the
components of the bovine, porcine,
canine and equine pituitary glands.
1 - pars tuberalis, 2 – pars distalis,
3 – adenohypophyseal cleft (cavum
hypophysis), 4 – pars intermedia,
5 – pars nervosa, 6 – recessus of third
ventricle
17.2. Pineal gland
The pineal gland (epiphysis) develops as a dorsal neuroepithelial diverticulum of the roof of
the diencephalon. The gland remains attached to the diencephalon by a stalk. The
neuroepithelial cells differentiate into pinealocytes, which synthesize and release melatonin,
and glial cells.
17.3. Adrenal gland
The paired adrenal glands develop from two different embryonic tissues, neural crest
ectoderm and coelomic epithelium. While in the lower animals exist as two separate
endocrine glands (fish) or are randomly integrated (reptiles, birds), in mammals the neural
crest derived tissue occupies a central position, surrounded by the tissue derived from
splanchnopleural mesoderm. Thus, the typical histological appearance of the mammalian
adrenal gland consists of an inner medulla and outer cortex.
Medulla - neural crest cells migrate toward the coelomic cavity wall and form the adrenal
medulla. (Fig. 17.3) The adrenal medulla resembles a modified ganglion of the sympathetic
169
nervous system but with cell bodies devoid of axons. Due to the affinity of cells for
chromium, which stains the cells brown, the cell bodies of the adrenal medulla are termed
chromaffin cells. In response to activation of the sympathetic nervous system, cells of the
adrenal medulla secrete epinephrine and norepinephrine.
Cortex - coelomic epithelium cells medially from the genital ridge proliferate initially
forming small buds that separate from the epithelium. Later these aggregations of mesodermal
cells which are located along the ventro-medial border of the mesonephros become organised
into cord-like structures. Neural crest cells migrate to a central position within the
mesodermal mass forming the adrenal medulla. Proliferating mesodermal cells of outer layer
form the adrenal cortex which is referred to as the foetal cortex. Subsequently, a second
proliferation of mesodermal cells surrounds the foetal cortex and postnatally becomes the
definitive cortex as the foetal cortex regresses. After birth, the definitive cortex differentiates
into three zones, the zona glomerulosa seu arcuata, the zona fasciculata and the zona
reticularis. (Fig. 17.3)
Figure 17.3 Formation of the adrenal gland. A, B – the arrows indicate growth of
primordium of the adrenal cortex and course of migration of neural crest cells, C – definitive
adrenal gland with three-layer cortex and medulla. 1 – neural crest, 2 – primordium of adrenal
cortex, 3 – migrating neural crest cells, 4 – gut, 5 – medulla, 6 - cortex
170
17.4. Thyroid gland
The thyroid gland develops as a ventral midline endodermal diverticulum from the floor of
the foregut at a level between the first and second pharyngeal arches, which extends ventrocaudally into the underlying mesenchyme. This structure is called thyreoglossal duct (ductus
thyreoglossus). (Fig.17.4)
The development of the thyroid gland is described in connection with digestive system
development (Chapter 13, page 117).
17.5. Parathyroid gland
The parathyroid glands develop from the dorsal segments of the third and fourth pharyngeal
pouches. The dorsal part of the left and right third pharyngeal pouches gives rise to an
external parathyroid or parathyroid III gland. The primordium of each gland loses its
connection with the pharyngeal wall and is drawn caudally by the developing thymus. (Fig.
17.4) The dorsal segment of the left and right fourth pharyngeal pouches gives rise to an
internal parathyroid or parathyroid IV gland, which also loses its connection with the
pharyngeal wall.
Because parathyroid III glands are drawn caudally by the developing thymus, they finally
occupy a position caudolateral to the parathyroid IV glands. In horses, the primordia of the
parathyroid III glands are drawn more caudally then in other domestic species and their final
position is close to the thoracic inlet.
As a result of caudal migration of developing thyroid gland, the parathyroid IV glands usually
become attached to or embedded within the substance of thyroid gland. In pigs, the primordia
of parathyroid IV glands regress and only the parathyroid III develop.
The cells of parathyroid glands differentiate into cords of cells referred to as chief cells
(secrete parathormone). In humans, horses and ruminants moreover a second cell type, the
oxyphil cells, with unknown function can be observed.
17.6. Pancreatic islets
Within the pancreas, which develops from dorsal and ventral endodermal buds (Fig. 13.16),
the endodermal cells differentiate to both the exocrine acini and endocrine islets of
Langerhans.
Clusters of endodermal cells gradually lose their connection to the exocrine portion and
differentiate into particular cell types (α-cells, ß-cells and δ-cells, G cells and PP cells) each
with the capability of producing a specific endocrine secretion (the glucagon, insulin and
somatostatin, gastrin and pancreatic polypeptide ) respectively.
The distribution of cell types among pancreatic islets is not uniform as well as the distribution
of islets within the different anatomical regions of the pancreas. The species-associated
variations are observed.
171
A
thyroid
primordium
1
1
2
pharyngeal
pouches
2
pharyngeal
arches
3
B
3
cervical
sinus
4
4
auditory
tube and
tympanic
cavity
thyro-glossal
duct
body of
thyroid
palatine tonsil
parathyroid III
developing
thymus
ultimobranchial
body
parathyroid IV
C
foramen caecum
line of descent of thyroid
para
thyroid
III
parathyroid IV
thyroid
thymus
Figure 17.4 Development of the thyroid gland and parathyroid glands, the
thymus and associated structures. Modified from McGeady et al. (2006).
172
18 INTEGUMENTARY SYSTEM
The integumentary system consists of two morphologically and functionally different layers
and their associated appendages (hairs, skin glands, hooves, claws, horns, feathers). The
superficial layer, epidermis, has an ectodermal origin and is formed by the stratified
squamous keratinised epithelium. The deeper layers, the corium or dermis and subcutis,
consist of connective tissue and originate from the mesoderm.
18.1. Epidermis
The epidermis develops from the ectodermal cells covering the surface of the embryo. It
consists of a single layer of cuboidal cells resting on a basal lamina. This simple cuboid
epithelium starts to proliferate and gives rise to a superficial layer of flattened cells, the
periderm, and an underlying layer of cuboidal cells, the basal layer. Periderm is a unique
feature of developing epidermis; no similar structure occurs in the development of other
epithelia. The function of the periderm is not known, but is thought to be related to exchange
of water, sodium and glucose between the foetus and the amniotic fluid.
With further proliferation of the cells of the basal layer, firstly a third, intermediate layer is
formed. Newly generated cells push older cells towards the surface of the epidermis. Finally,
the epidermis acquires its definitive arrangement and four layers can be distinguished: the
basal or germinative layer (stratum basale), the spinous layer (stratum spinosum), the
granular layer (stratum granulosum) and the cornified layer (stratum corneum). (Fig. 18.1)
The basal layer contains the epidermal stem cells, which divide mitotically giving rise to the
next generation of stem cells that stay attached to the basal lamina and to the cells that leave
the basal layer, differentiate and shift up, forming stratum spinosum. The latter cells start to
produce keratin, which is arranged in form of prominent bundles of keratin filaments, which
converge on desmosomes, binding the cells to each other. During further migration the
keratohyalin granules begin to appear in the cytoplasm and become the prominent component
in the next layer, granular layer. Finally the cells become flattened, their nuclei are pushed to
one edge of the cells, and eventually the cells lose their nuclei.
These cells of the cornified layer, which are filled with keratin filaments, are termed
keratinocytes. The keratinocytes of cornified layer are continuously shed.
Differentiation of epidermis is controlled with a number of growing factors, e.g.
transforming growth factor-α (Tgf- α), which is produced by the cells of the basal layer and
acts as an autocrine growth factor, or keratinocyte growth factor (Fgf-7), which is produced
by the fibroblasts of the underlying mesenchyme.
In newborn human babies, the waxy or cheese-like white substance coating the skin is found.
This substance, vernix caseosa, is composed of sebum, cells that have sloughed off the
foetus’ skin and shed lanugo hair.
Some other types of cells, so called epidermal non-keratinocytes can be identified in the
developing epidermis:
Melanoblasts migrate into the dermis and the basal layer of epidermis from the neural crest.
They contain melanosomes with the brown pigment, melanin, which is transported to the
keratinocytes, by the process of cytokrine (intercellular) secretion.
Merkel cells are intraepidermal mechanoreceptors associated with afferent free nerve
endings. The origin of Merkel cells is still debated. Evidence from skin graft experiments in
birds implies that they are neural crest derived, but experiments in mammals now demonstrate
an epidermal origin.
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Langerhans cells arise from precursors in the bone marrow and invade the epidermis later in
the prenatal development. These cells are involved in the presentation of antigens. They
cooperate with T-lymphocytes to initiate cell-mediated response to foreign antigens.
Figure 18.1 Developmental stages of the epidermis and dermis. A - Single layer ectoderm
with underlying mesenchyme. B and C - Development of periderm. D and E - Formation of
multi layered epidermis. il – intermediate layer F - The epidermis at the late foetal stage
showing the typical layers of stratified squamous epithelium.
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18.2. Dermis (corium)
The dorsal dermis originates from the dermatomes of the somites, whereas lateral and ventral
dermis and dermis of the limbs derivate from the lateral somatopleural mesoderm. The
mesenchyme derived from the mesoderm differentiates into the loosely arranged connective
tissue. The mesenchymal cells are interconnected by tight junctions on their processes and
they secrete the amorphous intercellular substance rich in hyaluronic acid and glycogen. Later
these mesenchymal cells differentiate into fibroblasts, which form increasing number of
collagen and elastic fibers. The deeper layer of dermis becomes thicker, forming reticular
layer (stratum reticulare corii), which consists of dense irregular connective tissue. The
superficial layer remains looser and gives rise to the papillary layer (stratum papillare corii),
which is composed of loose connective tissue. Thickenings of the papillary layer (papillae)
project into the basal layer of the epidermis and alternate with downgrowths of the basal
layer, termed epidermal ridges.
18.3. Hypodermis (subcutis)
In most regions of the body beneath the dermis, mesenchymal cells form a layer of loose
connective tissue, the hypodermis or subcutis. The hypodermis consists of irregular bundles
of collagen fibers interspersed with elastic fibers and varying number of adipocytes. Porcine
fat in the hypodermis forms well-defined layer, the panniculus adiposus.
18.4. Epidermal appendages
In animals a number of highly specialised cutaneous appendages occur, including a variety of
glands (sebaceous, sweat, aromatic, and mammary glands), hairs, horns and antlers and
terminal phalangeal coverings (claws and hooves). The development of cutaneous epidermal
appendages results from a series of reciprocal interactions between the epidermis and the
underlying mesenchyme, which are controlled by the cascade of proteins in the FGF and Wnt
signalling pathway.
18.4.1. Hair
Hairs are epidermal derivatives that cover the entire body surface of the domestic animals,
with exception of the muzzle, muco-cutaneous junctions and digital pads. They arise from the
epidermis as the result of inductive stimuli from the dermis. The first primordia of hairs
appear on the head of the foetus, around the lips, periorbita and lower jaw.
The formation of hairs begins during the early foetal period by the formation of solid
proliferations from the basal layer of the epidermis. This proliferation, the hair bud, projects
into the underlying mesenchyme at an oblique angel. An aggregation of mesenchymal cells,
known as the hair papilla, projects into the tip of the bud. The epidermal cells of the bud
grow around the hair papilla like an inverted cup, forming the hair bulb. The structure
formed from the hair bulb, together with the hair papilla, is referred to as a hair follicle. Soon,
cells in the centre of the hair bud become spindle-shaped and keratinized. They form the hair
shaft. The cells at the periphery of the hair bud remain more cuboidal and later develop into
the inner and outer epithelial root sheath. The mass of epidermal cells which gives rise to
the hair shaft and epithelial root sheaths is known as the germinal matrix. Finally, around the
outer epidermal hair sheath the surrounding mesenchyme forms a dermal (fibrous) root
sheath. (Fig. 18.2)
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Figure 18.2 Development of the hair
follicle. A - hair primordium, B - hair
bud, C - hair bulbe, D – growth of the
hair shaft and spacing of the hair follicle,
E – mature hair follicle with developed
sebaceous and sweat gland and arrector
pili muscle.
1 – epidermal proliferation
2 – mesenchyme
3 – hair papilla
4 – root of hair
5 – sweat gland primordium
6 – sebaceous gland primordium
7 – hair shaft
8 – arrector pili muscle
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Continued proliferation of the basal cells of the germinal matrix forces the hair shaft towards
the surface of a skin. The cells above its tip make way – hair canal, from which the hair
subsequently projects. Due to this movement of the cells away from the papilla, the cells
devoid the source of nutrition and undergo keratinization.
Primordia of the sebaceous and sweat glands form as cellular outgrowths from the basal
layer of the walls of developing hair follicles. Arrector pili muscles are derived from
mesenchymal cells in the dermis.
Hair follicles can be classified as either primary or secondary. The bulbs of primary hair
follicles have a large diameter and they are located deeper in the dermis. A single hair, so
called guard hair emerges from a primary follicle, which is associated with arrector pilli
muscle, sebaceous and sweat gland. Initially, primary hairs are evenly spaced. Later, new
primary follicles develop among them, resulting in groups of several hairs in close proximity
to each other. Subsequently, relatively small hair follicles, which are located more
superficially in the dermis, develop. Hairs which emerge from these secondary follicles are
referred as secondary or under hairs. Unlike primary follicles they lack sweat glands and
arrector pilli muscles.
Hair follicles may be also described as simple and compound. From the simple follicle only
one hair emerges. In the compound follicle, several secondary buds develop from the wall of
primary follicle in a manner analogous to the development of primary buds. Thus clusters of
hairs project from the skin surface through a common pore. (Fig. 18.3) In dogs and cats,
compound hair follicles develop postnatally.
Figure 18.3 Compound hair
follicle with primary hair and
associated secondary hairs.
1 – primary hair
2 – secondary hair
3 – epidermis
4 – sebaceous gland
5 – secondary hair follicle
6 – primary hair follicle
7 – hair papilla
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18.4.2. Sinus hair (sensory or tactile hair)
Sinus hairs follicles are located primarily in the head region, especially on the lips, cheeks and
chin and above the eyes, in cat are also present at the carpal region. During foetal
development, sinus hair follicles appear earlier than normal hairs, but they evolve later.
Initially, sinus hair follicle development is similar to primary hair follicle development.
However later, the sinus hair follicle rapidly enlarges and extends deep into the subcutis. The
characteristic feature of sinus hair follicle is the development of blood sinuses within the
dermal connective tissue sheath, which separate this sheath into an inner and outer layer. Free
nerve endings, which ramify especially within the inner layer of the dermal connective tissue
sheath, are responsible for the sensation of blood pressure changes inside the blood sinuses,
caused by the change of hair position. (Fig. 18.4) Skeletal muscle attached to the outer dermal
sheath enables a certain degree of voluntary control over tactile hair orientation.
Figure 18.4 Tactile hair follicle.
1 – outer layer of the dermal
connective tissue sheath
2 – inner layer of the dermal
connective tissue sheath
3 – inner epithelial sheath
4 – blood sinuses
5 – poorly developed sebaceous gland
(sweat gland doesn´t develop)
6 – outer epithelial sheath
7 – hair bulb
8 – sensory nerve fiber
18.4.3. Hair growth cycle
The cycle of hair growth involves an active phase of production, anagen, during which the
hair grows in length by addition of cells differentiating from the germinal matrix to the
bottom (deep) end. At some point, influenced by a number of factors, this stage ends and is
replaced by catagen, the stage of quiescence and cessation of new hair cell production.
The catagen phase is a short transition stage (2–3 weeks) in which the hair converts to a club
hair. A club hair is formed when the part of the hair follicle which is in contact with the lower
portion of the hair becomes attached to the hair shaft. This process cuts off the hair from its
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blood supply and from the cells of germinal matrix. Club hairs are not anchored in so they fall
out very easily. During telogen, the hair follicle becomes shorter, and it remains attached by a
cord of epithelial cells to the regressing hair papilla. Subsequently, a renewed anagen stage
commences, which leads to the formation of a new replacement hair. The epithelial cord gives
rise to a new hair bulb, which caps the newly developing papilla. As the new hair extends
towards the surface, it gradually displaces the old hair on the surface, where it is shed. (Fig.
18.5)
Figure 18.5 Sequential stages in the hair development
18.4.4. Skin glands
18.4.4.1. Sebaceous glands
As mentioned above, sebaceous glands develop from the wall of developing hair follicle as
lateral outgrow of the basal epithelium of the outer epithelial root sheath below the level of
sweat gland primordium. (Fig. 18.2) Sebaceous glands usually develop later than sweat
glands.
The solid swellings become lobulated to form alveoli, the clusters of which open into a single
short duct. As a consequence of repeated mitotic division the basal cells of alveolus give rise
to cells which migrate into the centre and fill the alveolar lumen. After that these cells
enlarge, accumulate lipid droplets, nuclei become pycnotic and disappear and cells break
down, forming sebum. Sebum is discharged through short ducts into the lumen of the hair
follicles. This mode of secretion is termed holocrine.
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Sebaceous glands are numerous and well developed in cattle, horses, dogs and cats, while in
pig are generally sparse and inconspicuous. Sebum has an antibacterial and antifungal effect,
maintains the skin in a pliable state and enhances its water repelling properties. In some
domestic species, well developed specialised sebaceous glands are accumulated in defined
regions of the body. They are referred as aromatic glands. These include glands in the
infraorbital, inguinal and interdigital regions of sheep, base of horn glands in goats and
paranal and circumanal glands of carnivores. Additionally, in birds, there is the uropygeal or
preen gland (glandula uropygii) located just above the base of tail, which produces a special
oily secretion that the bird spreads over the feathers.
18.4.4.2. Sweat glands
Based on their modes of secretion, mammalian sweat or sudoriferous glands can be
subdivided into two types: apocrine and eccrine (merocrine) sweat glands.
Apocrine sweat glands develop as nodular outgrows of the basal layer of the epithelium of
the hair follicle closer to the skin surface than sebaceous glands. Therefore they open into the
hair canal above the sebaceous glands. (Fig. 18.2) The solid cellular proliferation extends
deep into the connective tissue and the base of the gland may be located below the level of the
hair bulbs. The distal end of the gland may be coiled or spiral. A lumen develops firstly in the
distal region and later extends to the site of origin of the gland and opens into the hair follicle.
Apocrine sweat glands are the principal sweat glands in animals, in contrast to the situation in
human, and the distribution of them varies among animal species. Secretions of apocrine
sweat glands are relatively viscous with scent characteristic for individuals or species.
Eccrine glands develop as solid downgrowths of the basal layer of the epidermis, penetrating
into the underlying mesenchyme. The distal segment becomes coiled; the lumen develops and
extends proximally. The lumen of the intraepithelial portion of the duct forms by the
separation of cells. On the body surface their openings are visible as the small pores. In
humans, eccrine sweat glands are predominant while in domestic animals they are confined to
the footpads of carnivores, the frog of equine hooves, porcine snouts and bovine muzzles.
18.4.5. Development of the mammary gland
Mammary glands are specialized sweat glands. In domestic animals, mammary glands
develop from the paired epithelial thickenings on the ventral body wall of the embryo, the
milk lines or mammary ridges (lines), which extend from the axillary region to the inguinal
region. These glands have the same basic structure in all mammals. The mammary gland is a
compound tubuloalveolar gland demarcated by connective tissue into lobes and lobules. Milk
(lac), the secretion of this gland, is synthetized in specialised epithelial cells, which are
organised into small sacs, alveoli. Secretions are released into a duct system, which leads to
the surface of the body. The number of glands and their localisation vary with individual
species of mammals. In some of them all the milk line remains and develops in several
papillae (teats, nipples) with several gland openings in each teat (bitches, queens, sows). In
others the milk line is partially, cranially or caudally reduced and only one or two glands
develop on each side (cows, sheep, goats, mares, primates). In the small ruminants only a
single gland develops on each side with openings at the tip of papilla. In horse two glands
develop on each side, however both glands open on a single papilla. In cow two single glands,
each with a single papilla, develop in the inguinal region of mammary ridge on each side. In
primates there is one pair of mammary glands, also known as mammae, or breasts.
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Focal thickenings of epidermis appear at specific intervals along the mammary ridge and give
rise to the primary mammary buds. The primary bud pushes into the underlying
mesenchyme and grows, subsequently forming secondary mammary bud. The mammary
buds are initially solid cords of epithelial cells, later they canalise, form lactiferous ducts and
open onto the surface. These secondary buds lengthen and branch during the next embryonic
development and later during puberty in response to circulating hormones. Estrogen promotes
branching and differentiation, whereas in males testosterone inhibits it.
Secretory alveoli develop mainly in pregnancy, when rising levels of prolactin and estrogen
cause further branching and progesterone stimulates formation of alveolar framework,
together with an increase in adipose tissue and a richer blood flow.
18.4.5.1. Development of the bovine mammary gland
Pre-natal development of the bovine mammary gland begins in the inguinal portion of the
mammary line, caudal to the umbilicus. Two epidermal thickenings, mammary crests, form
on each mammary line. Their development is induced by the underlying mesenchyme.
Subsequently both mammary crests differentiate to two buds, separated from the
mesenchyme by well-developed basal membranes. (Fig. 18.6 A, B) During this stage of
development cranial portions of the mammary line not incorporated into the mammary crest
regress.
Up to the bud stage, the process of mammary development is the same in male and female
embryo. Thereafter, the male bud stays spherical, while in the female embryo the mammary
bud elongates and becomes ovoid with its long axis. Proliferation of the surrounding
mesenchyme causes outward projection of the tissue forming a conical papilla or primitive
teat.
The epidermal cells of the bud proliferate deep to the mesenchyme, forming club shaped
structure referred to as primary sprout. Its wider terminal portion is named bulb of the
primitive sprout. Later, the primary sprout becomes canalised at its proximal end, forming
the gland sinus or lactiferous sinus (sinus lactiferus). As the canalisation continues towards
the distal end of the primitive teat, the teat sinus (teat cistern) and papillary duct (ductus
papillaris) develop. (Fig. 18.6 D – I) The vascular supply, muscle and connective tissue
components of the teat are of mesenchymal origin.
When canalised, the secondary sprouts radiate from the wall of the gland sinus into the
surrounding tissue. Later in the development they give rise to lactiferous ducts draining the
glandular lobes.
Sustained mesenchymal development results in incorporation of the four glands into the
distinct anatomical structure referred to as the udder. Surrounding mass of mesenchymal cells
differentiates into adipose tissue, which forms adipose pads at the base of mammary gland,
the suspensory apparatus, smooth muscle cells and septum dividing the udder into left and
right part.
Postnatal development continues during the puberty, when estrogens promote the
development of the duct system and progesterone promotes the development of the secretory
glandular tissue. The glandular secretory tissue development accelerates in pregnancy.
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Figure 18.6 Sequential stages in the development of bovine mammary gland. A – cross
section through mammary crest, B - cross section through mammary bud, C – teat
primordium formation, D, E – formation of the primary sprout, F, G – canalisation of the
primary sprout, H – formation of the secondary sprouts, I – canalisation of the secondary
sprouts and formation of the definitive gland sinus (lactiferous sinus), papillary duct (ductus
papillaris and teat (papilla mammae). 1 – mesenchyme, 2 – ectoderm, 3 – mammary crest, 4 –
mammary bud, 5 – connective tissue stroma, 6 – primary sprout, 7 – bulb of primary sprout, 8
– epithelial depression, 9 – gland sinus, 10 – canalisation of the primary sprout, 11 –
secondary sprouts, 12 – canalisation of the secondary sprouts resulting in formation of ductuli
lactiferi, 13 – papillary duct
18.4.6. Hooves and claws
In mammals, the extremities of the limbs are modified in various ways for the protection of
the underlying tissues. The feet of animals reflect evolutionary changes involving epidermis,
dermis and hypodermis, bones tendons and ligaments of the pedal region and exhibit
considerable variety of distal limb integumentary appendages. The primordium of all digital
organs is similar but further differentiation varies considerably and leads to the digital organs
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characteristic of animal species. Based on the form of their digital organs, domestic animals
may be divided into two groups, the unguiculates or clawed animals (carnivores) and
ungulates or hoofed animals (horses, ruminants and pigs). Both hooves and claws are formed
by the modified keratinised epidermal capsule enclosing the underlying tissues of the digital
organ.
18.4.6.1. Equine hoof
During the early foetal development, firstly thickened area of epidermis appears on the dorsal
and lateral surfaces of the third digit. The thickened epidermis covers a thin layer of dermis up
to the end of the second month of gestation. During the third month of the foetal development,
the connective tissue of the dermis proliferates at the junction of the haired skin and hoof,
forming a proximal slightly elevated cushion (perioplic cushion) and distal more prominent
elevation (coronary cushion). On the ventral surface of the third digit the hypodermis
increases in depth, giving rise to the shock-absorbing digital cushions, from which frog and
bulbs develop. (Fig. 18.7) Thus at this stage of development all typical hoof-shaped
structures, wall, bars, sole, bulbs and frog has the morphological characteristics of the
matured hoof.
During the next development, a papillary body is created, consisting of the epidermis and
dermal papillae and ridges formed by outer layer of dermis. This ridged conformation may
be found in all animal species, but later undergoes species-specific differentiation.
Development of the papillary body in the equine hoof starts with increased mitotic activity of
the epidermal basal cells. The epidermal buds, presumably guided by the arrangement of
capillaries in the underlying tissue, invaginate into the dermis. Thus the complex of dermoepidermal interdigitations is established.
Further development of the papillary body is segment specific. Dermal papillae are
established in the dermis of the perioplic and coronary cushions as well as in the dermis of the
sole, frog and bars. Dermal ridges rise by the fusion of individual papillae arranged in rows
running from the distal part of the coronary cushion till the weight- bearing edge of the hoof.
These dermal ridges or primary laminae consist of the dermal core from which 100 – 200
secondary laminae originate at right angles. They are covered by the basal layer of
epidermis. By the proliferation of these basal epidermal cells the internal lamellar layer of
the horny hoof wall, the stratum internum, is formed.
The dermis of the coronary cushion forms hook-like, cone-shaped dermal papillae covered
by epidermis. Growth of the epidermal papillae is parallel to the long axis of the third
phalanx. By the proliferation of the basal epidermal cells at the apex and side wall of the
conic papilla, epidermal tubules are formed, that grow distally towards the weight-bearing
edge. This manner of development is comparable to hair shaft development.
These epidermal horny tubules consist of a hollow central medulla containing cellular debris,
and outer dense cortex of keratinised cells. The basal epidermis cells in inter-papillary areas
proliferate and form intertubular horn, which fills the spaces between the horny tubules. The
horn from the coronary cushion builds the intermediate layer of the hoof wall, the stratum
medium.
Close to the eighth month of gestation, epidermal cells on the surface of the perioplic
cushion proliferate and form long, thin hooked-shaped epidermal papillae. They form the
layer of soft tubular and intertubular horn, which extends over part of the surface of the
hoof wall, imparting a glossy appearance of the wall. This outer layer of the hoof wall, the
stratum externum, is also named tectorial membrane. Soft horn originating from the
perioplic epidermis also covers the bulbus of the heel.
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Due to the persistence of the periderm during hoof development, the proliferating epidermis is
initially soft and forms a cushion-like structure covering the tip of each hoof. This soft horn,
referred to as the eponychium, prevents damage to the amnion during foetal movements in
late gestation. The eponychium wears off quickly after birth.
Figure 18.7 Hoof of equine foetus. 1 – middle phalanx, 2 – distal phalanx, 3 – distal
sesamoid bone, 4 – perioplic cushion, 4a – coronary cushion 5 – digital cushion, 6 – epidermis
limbi (periople), 7 – sole papillae, 8 – bulb, 9 – frog, 10 – eponychium, 11 – hairy skin
18.4.6.2. Ruminant and porcine hooves
The manner of development of the ruminant and porcine hooves is analogous to that in
horses. The general structure of a hoof in even-toed ungulates also resembles to that of the
equine hoof, consisting of a wall, sole and prominent bulb. The main difference is that in the
ruminant and porcine hooves neither frogs nor bars develop. More over the secondary
lamellae are missing.
18.4.6.3. Canine and feline claws
In domestic carnivores, the claw is composed of a hard keratinised layer of modified skin,
which encloses the distal phalanx. The claw, consisting of a wall and sole, is evidently curved
and its shape corresponds to the shape of enclosed phalanx. The segment specific papillary
body is poorly developed compared with more specialised equine form and it is not able to
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transmit tension and compression forces as the weight-bearing apparatus of the equine hoof. It
serves especially for diffusion of nutrients to epidermal cells. Dermal ridges occur only over
the dorsal surface of the distal phalanx. Consequent on the high vascularisation of the corium,
damage to this structure from close clipping of the claws results in haemorrhage. A fold of the
skin referred to as the claw fold covers the proximal region of the claw. (Fig. 18.8) The outer
surface of this fold is formed by the normal hairy skin, while the proliferating cells of the
inner surface, which is hairless, produce a thin layer of keratinised cells which cover the
proximal region of the claw in a manner similar to the stratum externum of the equine hoof.
Fig 18.8 The canine foot – longitudinal section through the canine foot showing relationship
of structures. Cross section through claw at the level indicated.
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18.4.7. Horns
The horns of domestic ruminants are formed by paired bony cornual processes, which are
covered by a modified, highly keratinised skin without glands and hairs. Bovine horn
primordia firstly appear at the end of the second month of gestation as epidermal thickenings
in the frontal region of the head, surrounded by grooves and covered with hair. They are
usually observable in both sexes. The hairs around the horn primordia are longer and appear
whirl-like arrangement. Next development may be observable approximately one month after
birth, when epidermal cells of horn primordia proliferate forming cone-shaped horn buds.
Soon afterwards, frontal bone gives rise to bony outgrowths which form the osseous ground
of horns. During the following month, the solid bone base becomes hollow and the frontal
sinus extends into the horn cavity. (Fig. 18.9)
The dermis covering the cornual processes is fused with the periosteum and wears apicallydirected papillae covered by the keratinised epidermis. Proliferation of the epidermis gives
rise to horny tubules above papillae and intertubular horny tissue in inter-papillary
regions. Soft horn produced at the base of the cornual process is named horn sheath or
epiceras and it is adequate to the external layer of the equine hoof, which is produced by the
periople.
The periods of normal growth of horns may be alternated by periods of less intense growth
depending on conditions. During the pregnancy, stress or disease reduction of growth is
reflected in groove formation on the horn. In cows according to the so called pregnancy
grooves the age may be estimated.
Antlers of deer are horn-like structures. These branched outgrowths of scull bone have a skin
covering, referred to as velvet, (Fig. 18.9) and they undergo the annual growth, maturation
and shedding. The bone of antlers develops by the endochondral ossification. At the end of
the breeding season, components of the bone at the base of the antlers are resorbed and the
structures break off, leaving bony pedicles, the sites of future antlers re-growth.
Figure 18.9 Longitudinal section through a bovine horn (A) and through velvet-covered
antler of a deer (B)
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19 NERVOUS SYSTEM
The central nervous system and peripheral nervous system develop from the ectoderm. At
the end of the third week of embryonic development in domestic animals the notochord
induces multiplication of the overlying ectodermal cells of the embryonic disc and formation
of the pseudostratified neuroepithelium of the neural plate. Thus the ectoderm becomes
specified to the surface ectoderm and neuroectoderm.
19.1. Neurulation
Neurulation is the process, which leads to the formation of the neural tube, the precursor of
the central nervous system. Conventionally, the process of neurulation is divided into
primary and secondary phases.
The first morphological sign of primary neurulation is differentiation of the neural plate,
axially in anterior portion of the germ, which is induced by the underlying notochord. The
cranially expanded wider region of the neural plate forms the primordium of the brain,
while the narrower caudal region gives rise to the neural tube, the primordium of the spinal
cord. Shortly after the formation of the neural plate the lateral edges give rise to two lateral
elevations, the neural folds. The depressed midline region of the plate forms the neural
groove. Cellular proliferation at the medial aspects of the neural folds causes these structures
to gradually approach each other in the midline, meet and fuse, forming the neural tube
which encloses the central neural canal. Closure of the neural tube commences at the level of
the forth somite and from this point expands cranially and caudally until only small areas of
the tube remain open at both ends. (Fig. 19.1) Here the neural canal communicates freely with
the amniotic cavity. The cranial opening, the rostral neuropore, closes in the bovine embryo
at approximately Day 24 (18 to 20 somite stage), whereas the caudal neuropore closes two
days later (25 somite stage). As the developing brain and spinal cord have a limited vascular
supply at this stage of their development, it has been supposed that these structures receive
their supply of nutrients from the amniotic fluid through the neuropores. Closure of the
neuropores coincides with the establishment of the blood vascular circulation for the neural
tube.
The walls of the neural tube thicken to form the brain and the spinal cord. The neural canal
forms the ventricular system of the brain and the central canal of the spinal cord.
Formation of the neural tube in the sacral and caudal regions of the developing embryo occurs
through a process referred to as secondary neurulation. This is a different mechanism,
without neural folding, in which the spinal cord initially forms as a solid mass of
mesenchymal cells derived from the primitive streak. This solid cord fuses with the closed
caudal end of the neural tube. A central canal in the cord develops secondarily by cavitation
and becomes continuous with the neural canal formed during primary neurulation. The length
of the caudal region of the spinal cord correlates with the number of caudal vertebrae, and
accordingly is relatively long in animals with long tails and short in higher primates.
During the neurulation, the proliferation is also accompanied by some level of apoptosis in
the neuroepithelium. Apoptosis at tips of the neural folds during their adhesion serves to the
epithelial remodelling in midline and thus breaks the continuity between the neuroepithelium
and surface ectoderm. Inhibition of apoptosis or imbalance of the process of apoptosis and
neuroepithelial cells proliferation produces spinal neural tube defects, such as spina bifida
(incomplete closure of the neural tube).
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1
2
4
10
3
8
9
9
6
6
5
10
10
7
7
Figure 19.1 Development of the neural tube. 1 - surface ectoderm, 2 - neural plate, 3 neural folds, 4 - neural groove, 5 - neural tube, 6 - cranial neuropore, 7 - caudal neuropore, 8
- primitive node, 9 - primitive streak, 10 – somites. Modified from McGeady et al. (2006).
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19.2. Neural crest
During fusion of the neural folds, a population of specialised cells derived from the
neuroepithelium develops along the lateral margins of the neural folds at the interface
between the neural and surface ectoderm. (Fig. 19.2) The instruction is probably mediated
by gradient of bone morphogenic proteins, Bmp-4 and Bmp-7 together with Wnt-6 secreted
by surface ectoderm. When induced by these factors, the neuroepithelial cells change their
characteristics to those of mesenchyme-like cells and penetrate the basal lamina of the neural
plate (epithelio-mesenchymal transition). In the presence of above mentioned factors the
expression of Slug and RhoB transcription factors is induced in these specialised cells. Both
Slug and RhoB are believed to have a role in neural crest migration, because they characterise
the cells, which break away from the developing neural tube.
The neural crest cells form cellular aggregations dorsolaterally from the developing neural
tube which extend along the length of the neural tube on either side. (Fig. 19.2) A single
pluripotent neural crest cell can differentiate into many cell types depending on its location
within the early embryo. Different concentrations of the Bmp and Wnt signalling factors can
influence their differentiation in becoming defined cell types.
Neural crest cell migration spatially related in the anterior part of the neural crest starts well in
advance of neural tube closure, while in the spinal cord region the migration does not begin
until several hours after spinal neural tube closure is complete.
Major derivatives of the cranial neural crest are:
- Sensory ganglia of cranial nerves, trigeminal nerve (V), facial nerve (VII),
glossopharyngeal nerve (IX, superior ganglion) and vagus nerve (X, jugular ganglion)
- Odontoblasts
- Parafollicular cells of thyroid
- Carotid body cells
- Connective tissue of eye, stroma of cornea, ciliary muscles
- Pharyngeal arch cartilages
- Dermis and hypodermis of face and neck
- Conotruncal septum and cardiac valves
- Stroma of pharyngeal epithelial derivatives
Derivatives of both cranial and spinal neural crest are:
- Schwann cells
- Arachnoid and pia mater
- Parasympathetic ganglia (ciliary, ethmoidal, sphenopalatine, submandibular, visceral)
- Enteric ganglia
- Satellite cells of sensory ganglia
- Melanocytes
Major derivatives of the spinal neural crest are:
- Spinal ganglia
- Ganglia of the sympathetic chain, coeliac and mesenteric ganglia
- Adrenal medulla
- Enteroendocrine cells
- Neurosecretory cells of heart and lungs
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1
2
3
4
5
3
6
3
6
Figure 19.2 Development
of the neural crest.
7
1 - surface ectoderm
2 - neural plate edges
3
3 - notochord
4 - neural folds
6
5 - neural groove
6 - neural crest
7
7 - neural tube
8 - neural crests, which are
3
segmented into groups of
cells giving rise to a
8
7
3
190
different cell types
19.3. Neural tube
The neuroepithelium of the neural tube differentiates by the process of neurogenesis (birth of
neurons); the process by which neurons are generated from neural stem and progenitor cells.
The neural tube presents the prominent structure of the anterior, cephalic portion of the
embryo.
Initially, the neural plate and the neural tube are composed of a single layer of
neuroepithelial cells. The neuroepithelial cells are highly polarized along their apical-basal
axis, which is reflected, for example, in the organisation of their plasma membranes. Certain
transmembrane proteins are present selectively in the apical plasma membrane (prominin-1).
At a very early stage of development an external and internal limiting membranes
(membrana limitans externa and interna) are formed along the outer and inner surface of
neuroepithelium. These membranes are extracellular acellular basement membranes,
composed of type-IV collagen, laminin, entactin, nidogen and fibronectin.
The cells of neuroepithelium multiply typically near the external limiting membrane and the
epithelium organizes into a pseudostratified. The nuclei appear in several layers due to
different heights of elongated neuroepithelial cells. DNA synthesis (S-phase) proceeds in
nuclei located near the basal membrane (external limiting membrane) of the epithelium.
During the prophase, nuclei migrate within the cytoplasm towards the inner surface of the
neural tube (internal limiting membrane) where the mitosis is completed.
With the beginning of the cellular differentiation during the fourth week of embryonic
development in domestic animals, a wall of the neural tube thickens. The series of
differentiating cells remain connected with cytoplasmic bridges. This tissue, within the range
between external and internal limiting membrane is called myelospongium. (Fig. 19.3) Due
to the intense proliferative activity of the cells, especially in the inner half of the wall, the
portion of the wall closer the lumen becomes more cellular than the outer part. The thicker,
more cellular layer is called ventricular zone and the thinner outer, less cellular layer, which
contains numerous elongated processes of the cells, is named marginal zone. The ventricular
layer still shows mitotic activity, however, with further development, the proliferating cells
become exhausted and differentiate to the ependyma, lining the central canal and ventricles
of the brain. The basal processes of the ependymal cells radiate into the marginal layer. The
reminder of the ventricular zone, which contains the postmitotic differentiating cells,
neuroblasts and spongioblasts (see later), is called the mantle or intermediate zone. So that
finally, the three typical layers of the neural tube wall are established: ependymal zone,
mantle zone and marginal zone. (Fig. 19.3)
The cells of the pseudostratified neuroepithelium are considered as multipotent stem cells.
The multipotency implies that the cell can undergo an unlimited number of cell divisions and
may give rise to numerous types of differentiated cells. Applied to the CNS, stem cells may
be multipotent or bipotent.
During the mitosis, the orientation of the mitotic spindle is important for the fate of the
daughter cells. If the cleavage plane is perpendicular to the apical surface of the neural tube,
the two daughter cells are multipotent, they slowly migrate towards the periphery of the
neural tube and they prepare for another round of DNA synthesis. If, on the other hand, the
cleavage plane is parallel to the inner surface of the neural tube, the two daughter cells have
completely different fates. One of them remains the multipotent stem cell and the second one
a more differentiated is a bipotent progenitor cell, which gives rise to either neuronal or
glial progenitor cells
191
Figure 19.3 Differentiation of the wall of the neural tube. 1 - external limiting membrane,
2 - internal limiting membrane, 3 - notochord, 4 - surface ectoderm, 5 - myelospongium, 6 marginal zone, 7 – ventricular zone, 7a - mantle (intermediate) zone, 8 - ependymal zone
The neuronal progenitor cells give rise to a series of neuroblasts. Firstly, the cells without
processes are an apolar neuroblasts. Next, bipolar neuroblasts possess two slender
cytoplasmic processes that contact both external and internal limiting membranes. After
retracting of the inner process the bipolar neuroblast becomes a unipolar neuroblast. The
unipolar neuroblasts accumulate a large amount of rough endoplasmic reticulum (Nissl
substance) in their cytoplasm and then begin to send cytoplasmic processes. At this point they
are known as multipolar neuroblasts.
The glial progenitor cells (spongioblasts, glioblasts) continue to undergo mitosis and give
rise to progenitors of type 1 astrocyte, progenitors of type 2 astrocyte, oligodendrocyte
progenitor cells and radial progenitor cells. Anatomically, the astrocytes can be divided
into protoplasmic astrocytes, found in the grey matter, and fibrous astrocytes, found in the
white matter. The formation of oligodendrocytes depends on the signalling molecule sonic
hedgehog (Shh) produced by the cells of notochord. The flat processes of a single
oligodendroglial cell in the central nervous system ensure the myelinisation of several nerve
fibers. Radial glial cells act as guide wires in the brain for migration of young neurons during
midpregnancy. When neurons are migrating along the radial glial cells, they inhibit their
proliferation. After neuronal cell migration the radial glial cells re-enter the mitotic division
and they can transform into the neurons or glial cells (astrocytes or oligodendrocytes).
Not all glial cells originate from the neuroepithelium. Microglial cells, which function as
motile macrophages are mesoderm-derived cells that enter the CNS along with vascular
tissue.
192
19.4. Development of the spinal cord
As described earlier, three zones develop in the wall of the neural tube: ependymal, mantle
and marginal zone. As the spinal cord matures, the mantle or intermediate zone becomes the
grey matter, where the cell bodies of neurons are located. The marginal zone contains axons
and dendrites, but not neural cell bodies and forms the white matter of the spinal cord.
Initially, during the spinal cord development, neuroblasts in the dorsal and ventral regions of
the mantle zone on both sides of the midline proliferate rapidly, to form the left and right
dorsal and ventral thickenings. The more prominent ventral thickenings are referred to as
basal plates. They are populated by neuroblasts which give rise to motor neurons (somatic
efferent nerve fibers) and autonomic neurons (visceral efferent nerve fibers). The dorsal
thickenings are referred to as alar plates. Neuroblasts of the alar plates differentiate to the socalled interneurons, which receive the sensory impulses from the skin, mucosa, connective
tissues and muscles (somatic or visceral afferent nerve fibers). Left and right longitudinal
grooves form along the inner wall of the central neural canal and each is referred to as a
sulcus limitans. These grooves demarcate the boundary between the dorsal sensory alar
plates and the ventral motor basal plates. The left and right alar plates become connected
dorsally over the central canal by the thin roof plate and both basal plates become connected
by the floor plate ventral to the central canal. (Fig. 19.4) The roof and floor plates do not
contain neuroblasts, only nerve fibers facilitating the connection of one side to the other.
Bilateral ventral bulging of the basal plates, as a consequence of proliferation and hypertrophy
of the cells, results in the development of deep medial groove of the ventral surface of the
spinal cord, referred to as the median fissure (fissura mediana ventralis). A less prominent
medial groove also develops dorsally. During this process the sulci limitantes disappear and
due to the central neural canal becomes reduced in diameter.
The mature spinal cord is organised similarly to the embryonic pattern. The basal and alar
plates become subdivided into somatic and visceral components, neural processes develop
and the grey matter obtains the typical shape of butterfly evident in the cross section of the
spinal cord. In addition, a small lateral protrusions of grey matter develop laterally between
the dorsal and ventral columns, range from Th1 to L2 vertebrae. These lateral horns contain
cell bodies of visceral efferent neurons. (Fig. 19.4)
Within the white matter of the spinal cord, longitudinally oriented bundles of ascending and
descending axons (funiculi) are present. Due to the prevalence of myelinated axons, this
matter has whitish appearance. The dorsal, lateral and ventral funiculi are separated by the
efferent spinal nerve roots radiating from the ventral horns and afferent roots entering into the
dorsal horns of the spinal cord.
At the end of embryonic period, changes in the relative position of the spinal cord and the
developing vertebral columns are observable. Initially, the spinal cord is the same length as
the vertebral canal with spinal nerves passing through the intervertebral foramina at levels
corresponding to their points of origin. Because the vertebral column and dura mater grow
more rapidly than the spinal cord, the caudal end of the spinal cord gradually comes to lie at
relatively higher levels, and in different species of domestic animals terminates at different
levels in the lumbo-sacral region. This disproportional growth forces the spinal nerves to run
obliquely from the spinal cord to their corresponding vertebral foramina. Accordingly, the
caudal extremity of the spinal cord tapers and forms a structure which is referred to as the
conus medullaris. Caudal to the conus medullaris, the terminal portion of the spinal cord is
composed of a cord-like strand of glial and ependymal cells, the filum terminale, which
attaches the conus medullaris to the caudal vertebrae. Bundles of nerves running posteriorly
are collectively referred to as the cauda equina.
193
Figure 19.4 Development
of the spinal cord.
1 - marginal zone
2 - mantle zone
3 - ependymal zone
4 - central canal
5 - alar plate
6 - sulcus limitans
7 - basal plate
8 - motor neuron
9 - dorsal root ganglion
10 - dorsal median septum
11 - roof plate
12 - dorsal gray horn
13 - lateral gray horn
14 - ventral gray horn
15 - floor plate
16 - ventral median fissure
17 - white matter
18 - trunk of spinal nerve
19 - ventral motor root
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19.5. Development of the brain
The anterior two-thirds of the neural tube develop into the brain. After the fusion of the neural
folds and the closure of the anterior neuropore, an expansion of the rostral end of the neural
tube gives rise to three primary brain vesicles, separated by grooves. The first, most rostral
is the prosencephalon or forebrain. The evaginations, optic vesicles, grow out from each
side of the prosencephalon. The second and third primary brain vesicles are the
mesencephalon or midbrain and rhombencephalon - hindbrain.
The prosencephalon partly divides into two vesicles, the telencephalon and diencephalon.
The telencephalon grows fast; the lateral walls soon become domed, presaging the future
cerebral hemispheres. The diencephalon remains smaller, located in midline and connected
to the laterally expanding optic vesicles. The mesencephalon does not divide. The
rhombencephalon divides into the anterior metencephalon and posterior myelencephalon,
future medulla oblongata, which connects the brain stem with the spinal cord. The
metencephalon gives rise to the pons Varoli ventrally and the cerebellum dorsally.
Finally there are five secondary brain vesicles. (Fig. 19.5)
The embryonic brain grows rapidly and bends ventrally with the head fold. This bending
gives rise to the cephalic flexure in the midbrain region and the cervical flexure at the
junction of the hindbrain and the spinal cord. Later, a dorsal flexure, the pontine flexure,
occurs between the metencephalon and the myelencephalon. (Fig. 19.5) This flexure results in
thinning of the roof of the hindbrain. The sulcus limitans extends cranially to the junction of
the midbrain and forebrain, and thus alar and basal plates are recognizable only in the
midbrain and the hindbrain. As the telencephalon expands dorsally and caudally, it overlies
the diencephalon and mesencephalon, forming the cerebral hemispheres.
19.5.1. Rhombencephalon (hindbrain)
The rhombencephalon consists of the metencephalon, which extends from the pontine
flexure to the rhombencephalic isthmus, and myelencephalon, the most posterior brain
vesicle. The cervical flexure demarcates the myelencephalon from the developing spinal cord.
Later at this level the first cervical spinal nerves leave the ventral horns as the roots of ventral
horns.
19.5.2. Myelencephalon
The myelencephalon gives rise to the medulla oblongata, and the development of this
structure is similar to that of the spinal cord. The medulla oblongata serves as a conduit for
tracts between the spinal cord and the higher regions of the brain. Moreover also contains
important centres for the regulation of respiration and heartbeat.
In the medulla oblongata, unlike the spinal cord, the walls splay laterally with alar plates
located lateral to the basal plates. This causes a pronounced distention of the roof plate and
widening of the canal to the fourth ventricle. (Fig. 19.6) The roof plate of the myelencephalon
(lamina tectoria ventriculi IV) consists of a single layer of ependymal cells covered by a
vascular layer of mesenchymal cells which form the pia mater. The combined ependymal and
vascular layers form the tela choroidea. Active proliferation of the tela choroidea establishes
a number of proliferations protruding into the fourth ventricle, so-called choroid plexus,
which produces the cerebrospinal fluid.
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prosencephalon
mesencephalon
rhombencephalon
A
mesencephalon
telencephalon
optic cup
diencephalon
mesencephalon
cephalic flexure
cervical flexure
rhombencephalon
optic cup
B
telencephalon
mesencephalon
pontine
flexure
metencephalon
telencephalon
diencephalon
optic
vesicle
diencephalon
optic cup
mesencephalon
telencephalon
metencephalon
C
myelencephalon
Figure 19.5 Early development of the brain. A – three vesicular stage in the brain
development, B – formation of the telencephalon and diencephalon, and cephalic and cervical
flexure development, C – formation of the metencephalon and myelencephalon, and pontine
flexure development. Modified from McGeady et al. (2006).
196
By reason that the alar and basal plates come to line the floor of the hindbrain like the pages
of an open book, the efferent areas of the basal plates become positioned medially to the
afferent areas of the alar plates. The cavity of the myelencephalon (future fourth ventricle)
becomes rhomboid shaped.
The basal and alar plates contain aggregations of neuron cell bodies named nuclei. (Fig. 19.6)
The basal plates contain three motor nuclei: the medially situated general somatic efferent
nuclei of cranial nerves VI and XII, the intermediate special visceral efferent nuclei of
cranial nerves VII, IX and X and the lateral general visceral efferent nuclei of cranial nerves
VII, IX and X.
Neuron cell bodies of the alar plates migrate into the marginal zone and form islets of grey
matter, the gracile nuclei medially and the cuneate nuclei laterally. Another group of
neuroblasts from the alar plates migrates ventrally and forms the olivary nuclei. (Fig. 19.6)
However other neuroblasts of the alar plates accumulate into nuclei that are arranged in four
columns at each side. From lateral to the medial, these are: special somatic afferent,
receiving impulses from the inner ear, general somatic afferent, receiving impulses from the
surface of the head, special visceral afferent, receiving input from the taste buds, and
general visceral afferent, receiving impulses from the viscera.
Figure 19.6 Development of myelencephalon. Cross sections showing changes in the
relative position of alar and basal plates in comparison with spinal cord and development of
nuclei. 1 – alar plate, 2 – basal plate, 3 – central canal, 4 – sulcus limitans, 5 – fourth
ventricle, 6 – ventral plate, 7 – tela choroidea, 8 – olivary nucleus, 9 – nuclei of basal plate,
10 – nuclei of alar plate
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19.5.3. Metencephalon
The metencephalon develops from the anterior portion of the rhombencephalon, initially, in a
manner similar to that of the myelencephalon. The lateral walls diverge so that the alar plates
are located laterally to the basal plates. Later during its development, the metencephalon
differs from the myelencephalon by forming two specialised structures, the dorsally
positioned cerebellum and ventrally located pons. The cerebellum functions as a
coordination centre for posture and movement, while the pons that is located cranial to the
medulla oblongata, caudal to the midbrain and ventral to the cerebellum, includes tracts that
conduct signals from the cerebrum down to the cerebellum and medulla, and tracts that carry
the sensory signals up into the thalamus. Each basal plate of the metencephalon contains three
groups of motor neurons: the medial general somatic efferent group, which forms the
nucleus of the abducens (VI) nerve, the intermediate special visceral efferent group, which
gives rise to the nuclei of the trigeminal (V) nerve and facial (VII) nerves, innervating the
muscles of the first and second pharyngeal arches, and the lateral general visceral efferent
group giving rise to the nucleus of the facial (VII) nerve, supplying the mandibular and
sublingual glands. Some alar plate neurons migrate ventrally to form pontine nuclei. Axons
from neurons in the cerebral cortex terminate on pontine nuclei, forming tractus
corticoponticus.
19.5.3.1. Cerebellum
The cerebellum develops from the dorsolateral regions of the alar plates, so called rhombic
lips. As a consequence of cellular proliferation, the rhombic lips meet and fuse in the rostral
region, forming the cerebellar plate over the fourth ventricle. In the early foetal period, this
cerebellar primordium expands dorsally, forming the dumb-bell structure with transverse
fissure dividing it into a larger anterior and smaller posterior portion. The larger cephalic
portion consists of narrow medial region, the vermis, connecting the lateral hemispheres.
(Fig. 19.7) The smaller posterior region consists of a pair of flocculo-nodular lobes. They are
considered to be the phylogenetically oldest structures of the cerebellum, which are associated
with the development of the vestibular apparatus.
The cerebellar vermis and the hemispheres undergo distinct growth and expansion. This
enlargement is characterized by marked folding of the surface, resulting in close, parallel,
transverse folds – the folia cerebelli.
During the early foetal period, cells of the neuroepithelium migrate through the mantle and
marginal layers to the surface of the cerebellum, where they are arranged into a second
germinal layer, the external germinal layer. Cells of this layer are still able to divide
mitotically and later give rise to various cell types, including granule cells, basket cells and
stellate cells. Some cells of neuroepithelium, now referred to as inner germinal layer, give
rise to neuroblasts which migrate deep into the cerebellar hemispheres forming four
cerebellar nuclei (nucleus dentatus, nucleus fastigii) which are responsible for relaying
signals to and from the cerebellar cortex. Cells from the inner germinal layer also migrate
towards the external germinal layer where they differentiate into Purkinje cells. Finally, the
inward migration of the external granule cells depletes the outer zone of cerebellar cortex and
establishes the definitive inner granule layer below a middle layer of Purkinje cells. The
outer zone becomes the molecular layer of the cerebellar cortex containing basket and
stellate cells.
198
Figure 19.7 Development of the
metencephalon - formation of the
cerebellum and pons.
1 – alar plate
2 – basal plate
3 – pons
4 – fourth ventricle
5 – vermis
6 – primordia of cerebellar
hemispheres
7 – primordial cerebellar plate
8 – rhombic lips
19.5.4. Mesencephalon
The mesencephalon (midbrain), in comparison with other portions of the brain, remains
structurally relatively simple. As result of the medial expansion of the alar and basal plates
into the roof and floor plates, the neural canal is reduced in size, forming mesencephalic
aqueduct (aqueductus mesencephali).
Neuroblasts of the alar plates form the tectum (the roof of the mesencephalon), dorsal to the
aqueduct, which differentiates into firstly two aggregations of nuclei, corpora bigemina, and
after that by the transversal groove into the corpora quadrigemina (paired rostral and caudal
colliculi). The paired rostral colliculi are associated with visual function and two caudal
colliculi with auditory function.
The tegmentum, which arises from the basal plates ventral to the aqueduct, contains the
efferent nuclei: the general somatic efferent and general visceral efferent nucleus of the
oculomotor nerve (IV) and general somatic efferent nucleus of the trochlear nerve (III).
Another nuclei, nucleus ruber and substantia nigra, involved in motor coordination are the
component of the corticospinal and the corticobulbar tracts. It is not still clear, whether the red
nuclei and substantia nigra are derived from the basal plates, or by migration of neurons from
the alar plates.
Neurons from the intermediate layer of both basal and alar plates contribute to the formatio
reticularis, an aggregation of the nerve cells located around the aqueduct. The marginal layer,
associated with each basal plate, enlarges considerably and forms crura cerebri (cerebral
peduncles) which serve as pathways for axons descending from the cerebral cortex to lower
centres in the metencephalon and spinal cord.
19.5.5. Prosencephalon (forebrain)
The prosencephalon, the most rostral of the three primitive brain vesicles, give rise to anterior
part, telencephalon, and posterior part diencephalon. The telencephalon forms cerebral
hemispheres and the olfactory bulbs. The diencephalon gives rise to the epithalamus,
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thalamus metathalamus and hypothalamus, as well as the optic cups, epiphysis and
neurohypophysis. The cavity developing within the diencephalon is the third ventricle and
the paired cavities within the telencephalon are the lateral ventricles. Because of the basal
plates are absent from the forebrain, all forebrain structures (telencephalon and diencephalon)
are formed from the alar plates and the roof plate.
19.5.6. Diencephalon
Development of the diencephalon is characterized by the appearance of three pairs of
swellings on the medial aspect of the lateral wall. They form a dorsal epithalamic, an
intermediate thalamic, and the ventral hypothalamic primordium on each side. Later, the
hypothalamic masses, originally paired, fuse forming a single structure, which differentiates
to a number of nuclei. They function as the regulatory centre for control of body temperature,
hunger, sleep, fluid and electrolyte balance, emotional behaviour and activity of the pituitary.
Paired subthalamic nuclei, the mammillary bodies, form distinct protuberances on the
midventral surface of the hypothalamus. Moreover, a ventral downgrowth from the
diencephalon forms the infundibulum of the neurohypophysis.
The thalamus and hypothalamus are demarcated by a hypothalamic sulcus.
The thalamus enlarges rapidly on each side and bulges into the cavity of the third ventricle. In
domestic animals these protrusions are so great that they fuse in midline, forming the
interthalamic adhesion. Due to the third ventricle becomes ring-shaped and ventral to the
adhesion forms a vertical slit extending into the infundibulum. Dorsal to the interthalamic
adhesion, the third ventricle is covered by the roof plate, reduced to a single layer of
ependymal cells and covered by vascular mesenchyme. These two layers form choroid
plexus of the third ventricle and the lateral ventricles. The most caudal portion of the roof
plate of the diencephalon forms small medial diverticulum, which develops into a coneshaped structure, the epiphysis or pineal gland.
Two side vesicles evaginate from the lateral walls of the diencephalon in early stage of its
development, the primordia of the optic cups.
The thalamus acts primarily as a centre for transmission sensory impulses, along with signals
from the cerebellum and basal ganglion, to the cerebral cortex.
19.5.7. Telencephalon
The telencephalon consists of a central portion, the lamina terminalis, and two lateral
diverticula, the telencephalic vesicles, the walls of which give rise to the future cerebral
hemispheres that completely overgrow the anterior parts of the brain stem.
The telencephalic vesicles extend initially in a rostral direction, later in a dorsal direction,
than caudally and finally in a ventral direction, assuming a C-shaped appearance. Thus in
their final form, the cerebral hemispheres are located over the diencephalon, mesencephalon
and the rostral portion of the hindbrain. (Fig. 19.8)
Telencephalic vesicles surround the expanding lateral ventricles, communicating with the
third ventricle by the interventricular foramina (Monroi). Initially during early pregnancy,
external surface (pallium) of the cerebral hemispheres remains smooth but later, they undergo
folding and several sulci (grooves) and gyri (elevations) develop. The external pattern of sulci
and gyri of the mature brain is species-specific. On the surface of the hemispheres is possible
to discern foundations of paired lobes (lobus frontalis, parietalis, occipitalis and temporalis).
The ventral parts of the hemispheres expand rostrally, forming bulbus olfactorius and
tractus olfactorius. The olfactory lobe (rhinencephalon) is relatively large in lower animals
but in higher becomes relatively small due to growth of neocortex.
200
mesencephalic aqueduct
fourth ventricle
metencephalon
myelencephalon
mesencephalon
diencephalon
third ventricle
telencephalon
lateral ventricle
interventricular
foramen
telencephalon
mesencephalon
mesencephalic aqueduct
metencephalon
fourth ventricle
lateral
ventricle
diencephalon
myelencephalon
third ventricle
interventricular foramen
telencephalon
rostral colliculus
caudal colliculus
mesencephalic aqueduct
cerebellum
fourth ventricle
lateral
vnetricle
pons
interventricular
foramen
diencephalon
myelencephalon
third ventricle
infundibulum
Figure 19.8 Sequential stages in the development of the forebrain and hindbrain.
Arrows indicate the direction of telencephalic vesicles expansion. Modified from McGeady et
al. (2006).
201
The medial walls of expanding hemispheres are separated by a longitudinal fissure, into
which grow mesenchyme, forming falx cerebri. During the late pregnancy, cellular
proliferation in the floor of each hemisphere gives rise to prominent swelling which bulges
into the lateral ventricles, forming corpora striata. They contain the complex of basal nuclei
(nucleus caudatus, nucleus lentiformis), which contribute to the control of muscle tension and
body movements. The complex of myelinated nerve fibers, which create corpus striatum and
course from the brain cortex to the thalamus, is capsula interna.
In the ventral portion of the medial wall numerous grooves referred to as choroid fissures
develop and project into the lateral ventricles. The thin ependymal layer together with
invaginations of vascular pia mater form the choroid plexuses of the lateral ventricles.
Through the interventricular foramina this structure passes into the third ventricle forming
choroid plexus of the third ventricle. (Fig. 19.9)
Dorsal to the choroid plexuses, the medial walls of the cerebral hemispheres become thicker,
forming the hippocampi. In mammals, the infoldings of the hippocampal regions into the
lateral ventricles form a specific gyrus. The hippocampus, which forms component of limbic
system, is closely associated with memory.
The functional development of the telencephalon begins by the radial migration of neuroblasts
during early stage of embryo development. The neuroblasts migrate from the ventricular
layer, where they origin, to the external surface of the telencephalic vesicles. There are
genetically predeterminated loci in the ventricular layer of the neural tube that are in relation
with particular areas on the surface of the hemispheres. Thus the neuroblasts originating at
given locus and developmental time will end up at defined points in the future cortex.
Migration of neuroblasts is ensured by the radial glial cells that extend from the ventricular
layer of the neural tube to the corresponding area on the surface of the hemisphere. The
neuroblasts move alongside their processes to their destinations. Moreover, the time of the
migration strongly influences the arrangement of neurons in the cerebral cortex. Three
sequential waves of cellular migration occur during the formation of the cerebral cortex, each
giving rise to a distinct layer. The first wave of migrating neurons constitutes the deepest or
third layer of cerebral cortex. Next neurons from the ventricular layer must migrate through
layers of neurons already established. In this manner firstly the deepest and then more
superficial layers are formed (inside-out layering of the cerebral cortex).
Once the neuronal cells have reached their final position, neural processes, firstly axonal,
and then dendritic, grow out from them to specific target cells along tightly guided paths. As
the cerebral cortex develops, axons of its neurons synapse to other neurons in the following
ways: 1) with neurons within the same hemisphere = association neurons
2) with neurons of other hemisphere = commissural neurons
3) with neurons of other regions of the brain and spinal cord = projection neurons
From the phylogenetic point of view, the cerebral cortex can be subdivided into the
evolutionary older allocortex, which comprises the archicortex (archipallium) and the
paleocortex (palaeopallium) and the newer neocortex (neopallium, isocortex). The allocortex
displays a wide variety of histological patterns in different regions, but generally consists of
three histological layers (molecular, pyramidal or granular, and polymorphic layer). The
neocortex, presents more complicated, five or six-layered histological structure, and it makes
up most of the cerebral cortex in higher animals.
During the early development the palaeopallium is pushed to the ventral surface of the brain,
where it becomes the olfactory lobes (rhinencephalon), while the archipallium, the oldest
region of the brain pallium, becomes rolled over at the medial dorsal edge to form the
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hippocampal formation. The rhinencephalon comprises the olfactory bulb, olfactory tracts,
olfactory tubercle and piriform lobe.
In carnivores, the major neuronal connections are completed by the third postnatal week but
full maturation is delayed until the sixth week or later, when myelinisation of the major
pathways has been completed. In precocial animals (ungulates, guinea pig, hare) the cortex
has already reached functional maturity by the time of birth.
1
2
7
3
4
8
10
9
5
11
6
Figure 19.9 Formation of the telencephalon. Cross section through forebrain showing the
relationships of the developing brain structures. 1 – falx cerebri, 2 - telencephalic vesicle,
3 – lateral ventricle, 4 – choroid plexus, 5 – roof plate of the third ventricle, 6 – choroid
plexus of the third ventricle, 7 – hippocampus, 8 - caudate nucleus, 9 – lentiform nucleus,
10 - corpus striatum, 11 – third ventricle
19.6. Meninges
The developing neural tube is surrounded by loose mesenchymal tissue. Subsequently, this
mesenchymal tissue condenses forming the protective coverings of the central nervous
system, the meninges. These coverings develop into an outer ectomeninx, derived from the
axial mesoderm, and an inner layer, the endomeninx, considered to be a derivative of the
neural crest cells. The ectomeninx forms the dura mater, a tough, connective tissue sheath
composed of collagen and elastic fibres. The endomeninx later subdivides into a thin pia
mater, which is closely apposed to the neural tissue, and a middle arachnoidea, a delicate
non –vascular layer.
The dura mater spinalis forms dural sac along the length of the spinal cord. The attachment
between the dura mater and vertebrae develops only on its cranial and caudal end. At its
cranial end, the dura mater is attached at the rim of the foramen magnum to the
periosteum of the skull. At its caudal end, the dura mater tapers from the tubular structure to
a dense cord-like structure composed of collagen fibres which blend with components of the
filum terminale, forming caudal (coccygeal) ligament, which fuses with the periosteum of a
caudal vertebra. The space between the dura mater and the wall of developing vertebral
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canal is termed the epidural space. (Fig. 19.10 B) This space contains loose connective
tissue, blood vessels and adipose tissue which provide additional support for the spinal cord
and for roots of the spinal nerves.
The dura mater of the brain is composed of two distinct layers formed by dense irregular
connective tissue. The outer layer fuses with the periosteum of the developing bones of the
cranium. That is why no epidural space exists within the range of the cranium. The inner layer
projects between the cerebral hemispheres, forming a large fold, the falx cerebri. (Fig. 19.10
A) Furthermore, a smaller transversal fold, the tentorium cerebelli, separates the cerebellum
from the cerebral hemispheres, and the inner layer of the dura mater which extends over the
surface of the pituitary gland is referred to as the diaphragma sellae.
The two layers of the dura mater run together and they separate only at points where the inner
layer projects into the major fissures of the brain. At these points the gaps between them are
called dural venous sinuses. The venous sinuses drain the blood and cerebrospinal fluid from
the brain into the internal jugular vein.
The endomeninx gives rise to the leptomeninges, the outer arachnoid membrane and the
inner pia mater. The arachnoidea consists of an outer layer of flattened fibrocytes and an
inner loosely arranged layer of connective tissue. The dura mater and the arachnoid
membrane are separated by the fluid-filled space referred to as the subdural space. While the
arachnoidea is non-vascular, the inner layer of the endomeninx, the pia mater, is a thin highly
vascular connective tissue layer, which is closely attached to the underlying nervous tissue by
reticular and elastic fibres and by the processes of astrocytes. This delicate vascular layer
follows the surface contours of the brain and projects into the sulci. Blood vessels in the pia
mater supply the nervous tissue. As they penetrate into the nervous tissue, they are covered by
the pia mater for a short distance. The fusion of small spaces in mesenchyme between the pia
mater and arachnoid membrane constitute the subarachnoid space through which the
cerebrospinal fluid circulates. The mesenchyme, which persists between the membranes,
forms trabeculae which attach the arachnoid membrane to the pia mater.
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Figure 19.10 Relationships of the meninges to adjacent structures in the brain region
(A) and spinal cord region (B)
19.7. Development of the peripheral nervous system
The peripheral nervous system consists of the cranial, spinal, and visceral nerves and the
cranial, spinal and autonomic ganglia. The peripheral nerves which conduct impulses away
from CNS are efferent or motor; fibers that conduct impulses from the periphery towards the
CNS are afferent or sensory. Nerves usually contain both types of fibers. The peripheral
nerves are the processes of neuroblasts of the mantle layer of the neural tube. Both types,
efferent as well as afferent nerves, can also be classified as being somatic or visceral. This
subdivision is based on whether a peripheral nerve terminates in tissue derived from the
splanchnopleure (i.e. visceral tissue), or somatopleura (i.e. body wall tissue).
All sensory cells (somatic and visceral) of the PNS develop from the neural crest cells. The
cell bodies of these sensory cells are located outside the CNS. With the exception of the
neurons of vestibular ganglion (vestibulocochlear nerve) and the cells in spiral ganglion of the
cochlea, all peripheral sensory neurons are originally bipolar, with a peripheral and central
process emerging from opposite sides of the soma. Later, the two processes approach and fuse
to form a single process of a pseudo-unipolar neuron. The cell bodies of afferent neurons
are invested by a capsule of modified Schwan cells – satellite cells, which are derived from
neural crest cells. This sheath is continuous with the neurolemma (sheath of Schwann) that
surrounds the axons of afferent neurons.
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19.7.1. Spinal nerves
The efferent nerve fibers arise from the neurons located in the basal plates of developing
spinal cord and form continuous series of rootlets along its ventrolateral surface. The nerve
fibers become arranged in bundles, forming ventral nerve roots.
The nerve fibers of the dorsal nerve roots are formed by axons derived from the neural crest
cells that migrate to the dorsolateral aspect of the spinal cord, where they differentiate into the
cells of the spinal ganglion. The central processes of these cells grow towards the dorsal
horns of the spinal cord and establish synapses with sensory interneurons located in this area.
The distal processes of the spinal ganglion cells grow towards the ventral nerve root and
eventually join it to form a mixed spinal nerve. Immediately after being formed, a mixed
spinal nerve divides into dorsal and ventral primary rami (branches). The dorsal rami of the
spinal nerves innervate the dorsal axial musculature, vertebral joints, and the skin of the back.
Ventral rami innervate the limbs and ventral body wall and form the major nerve plexuses.
The major nerve plexuses, cervical, brachial and lumbosacral are formed by secondary
branches of the ventral rami, joined by connecting loops of nerve fibers. The developing
plexuses supply the muscles and skin of the limbs. As the limbs develop, the nerves from the
corresponding spinal cord segments grow into the mesenchyme, elongate, and form
neuromuscular synapses with the developing muscle fibers. The dorsal divisions of these
plexuses supply the extensor muscles and the extensor surface of the limbs; the ventral
divisions supply the flexor muscles and flexor surface. The skin of the developing limbs is
also innervated by segmental nerves fibers.
19.7.2. Cranial nerves
Twelve pairs of cranial nerves develop in mammals. They can be classified into three groups,
according to their embryologic origins:
1) nerves with special sensory function (special somatic afferent or special visceral
afferent fibers)
2) mixed nerves of pharyngeal arches (special visceral efferent and afferent fibers)
3) somatic efferent cranial nerves with exclusively motor function
Nuclei of cranial nerves, except the olfactory (I) and optic nerves (II), arise from the brain
stem and only the oculomotor nerve (III) arises outside the region of the rhombencephalon.
By convention, roman numerals are used to designate the cranial nerves according to their
sites of origin in the brain, with cranial nerve I the most rostral and cranial nerve XII the most
caudal. Cranial nerves are also named in accordance with the regions or structures which they
innervate.
19.7.2.1. Special sensory nerves
Three cranial nerves, namely olfactory (I), optic (II), and vestibulocochlear (VIII) are
included in this group. The olfactory and optic nerves are often regarded to as extensions of
brain tracts than as true cranial nerves.
The neurons of the olfactory nerve develop from the nasal placode. Unmyelinated axons of
the olfactory neurons end in the olfactory bulb, where they form synapses with the mitral
cells.
The optic nerve is formed by nerve fibers that are derived from the ganglion cells of the
primitive retina.
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The vestibulocochlear nerve contains two kinds of sensory nerve fibers running in two
bundles, the vestibular and the cochlear nerves. The vestibular nerve is formed by axons of
the bipolar neurons of the vestibular ganglion. The cochlear nerve is formed by axons of the
bipolar neurons of the spiral ganglion. The dendrites of ganglionic cells innervate the
vestibular apparatus and Corti or spiral organ.
19.7.2.2. Mixed nerves of pharyngeal arches
Four cranial nerves, the trigeminal (V), facial (VII), glossopharyngeal (IX), vagus (X), and
in addition cranial root of the accesory nerve (XI) innervate pharyngeal arches derivatives.
These nerves contain both sensory and motor fibers.
19.7.2.3. Somatic efferent cranial nerves with exclusively motor function
The oculomotor (III), trochlear (IV), abducens (VI) and hypoglossal (XII) nerves can be
considered to be homologous with the ventral roots of spinal nerves. The corresponding
neurons are located in general efferent motor nuclei of the brain stem. Their efferent axons
supply the muscles derived from the preotic and occipital myotomes.
19.7.3. Autonomic nervous system
The autonomic nervous system is also referred to as general visceral efferent nervous
system. It regulates many of the involuntary functions of the body, such as the function of the
smooth muscle, cardiac muscle, exocrine glands and some endocrine glands.
Functionally, the efferent portion of the autonomic nervous system can be subdivided into the
sympathetic nervous system, originating from the thoracolumbal region, and the
parasympathetic nervous system, originating from the cranial and sacral regions. Unlike
the somatic efferent system which is single-neuronal system, the visceral efferent system is a
two-neuronal system. The cell body of the first, pre-ganglionic neuron is located in the
lateral horn of the grey matter of the spinal cord or equivalent nuclei of the brain. The second,
post-ganglionic neuron is in peripheral ganglion. All second neurons originate from the neural
crest and their axons are termed post-ganglionic axons.
In the sympathetic system, the first and second neurons use different transmitters. Preganglionic telodendria release acetylcholine whereas majority of the sympathetic second
neurons release norepinephrine at their terminals.
In the parasympathetic system, the first as well as the second neurons utilize acetylcholine as
the transmitter.
The autonomic nervous system also includes the general visceral afferent neurons and
interneurons in the brain and spinal cord.
19.7.3.1. Sympathetic nervous system
Towards the end of the embryonic period, neural crest cells on either side of the spinal cord
migrate to position lateral to the developing vertebrae where they form aggregations. From
these aggregations segmentally arranged paravertebral (sympathetic) ganglia develop,
which are interconnected by longitudinal nerve fibers forming the sympathetic trunk. Later,
these ganglia partially fuse, especially in the cervical region and form cranial cervical,
medial cervical and caudal cervical ganglion. The caudal cervical ganglia with the first
thoracic paravertebral ganglia give rise to the cervico-thoracic or stellate ganglion. (Fig.
19.11) Moreover, neural crest cells that migrate close the branches of the aorta that supply the
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abdominal viscera form preaortic ganglia, coeliac ganglion and the cranial and caudal
mesenteric ganglia.
After the sympathetic trunks have formed, the myelinated axons of the pre-ganglionic
neurons grow out from the lateral horns of the spinal cord alongside somatic efferent axons in
the ventral roots. The ventral roots join with the dorsal roots forming spinal nerves.
Immediately, after the spinal nerves emerge the intervertebral foramina the pre-ganglionic
myelinated axons form white communicating rami which penetrate into the paravertebral
ganglions, where they form branches. Some branches may synapse with post-ganglionic
neurons of the paravertebral ganglion, while other branches ascend or descend in the
sympathetic trunk to synapse with neurons of other paravertebral ganglia. Some preganglionic fibers bypass the paravertebral ganglia without synapsing and form the splanchnic
nerves to the pre-aortic ganglia. Other fibers, the grey communicating rami, run from the
sympathetic chain of ganglia to spinal nerves and from there to peripheral blood vessels, hair,
and sweat glands. Grey communicating rami can be seen at all levels of the spinal cord.
The axons of post-ganglionic neurons are non-myelinated and innervate target structures as
the splanchnic nerves. They typically release norepinephrine at their distal terminals.
19.7.3.2. Parasympathetic nervous system
Pre-ganglionic neurons of the parasympathetic system are located in distinct nuclei of the
brain stem, and also in the lateral columns of the sacral region of the spinal cord. Their axons
emerge from the brain stem as components of the oculomotor (III), facial (VII),
glossopharyngeal (IX), and vagus (X) nerves. The pre-ganglionic axons of the sacral nerves
create the pelvic nerve. (Fig. 19.11)
Parasympathetic pre-ganglionic fibers are long (longer than post-ganglionic), myelinated and
they ramify, forming 3 branches. As a consequence of the reduced branching of
parasympathetic pre-ganglionic fibers (in comparison with the branching of sympathetic
fibers), the effects of parasympathetic stimulation are more localised.
Because the post-ganglionic neurons are located in peripheral ganglia or plexuses near or
within the organs being innervated (e.g. the pupil of the eye, salivary glands, or viscera of
thoracic and abdominal cavity) the post-ganglionic non-myelinated axons are short. Most of
them release acetylcholine at their synapses.
19.7.3.3. Enteric nervous system
The enteric nervous system consists of neurons and their axons and supporting cells. The
neurons are derived from neural crest cells that originate in the rhombencephalic and sacral
region of the neural crest. The neural crest cells migrate into the wall of the developing gut,
forming two interconnected plexuses. The submucosal plexus (Meissner´s plexus) and the
submucosal ganglia are located in the submucosal connective tissue, and myenteric plexus
(Auerbach´s plexus) and myenteric ganglia are situated circumferentially between the inner
circular and outer longitudinal smooth muscle layers.
The reflex pathways of the enteric nervous system influence gastrointestinal motility
(peristaltic contractions), and secretion, transport of water and electrolytes across intestinal
epithelium and also blood supply to the intestinal mucosa.
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Figure 19.11 Schematic drawing of origin and arrangement of the sympathetic (A) and
parasymphatetic (B) nervous system. Virtually, a disposition of both nervous systems is
symmetrical. Modified from McGeady et al. (2006).
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20 SENSORY SYSTEM
The sensory system is a part of nervous system consisting of sensory receptors that receive
stimuli from internal and external environment, neural pathways that conduct the
information to the brain and parts of the brain that process this information.
The sensory receptors may be arranged into more or less complicated sensory organ: the
olfactory epithelium in the nasal cavity, taste buds of the tongue, sensory corpuscles in the
skin, the ear and the eye. Sensory organs are able better detect the stimuli. Many of the
sensory organs conduct information to the midbrain or the thalamus (except the smell). From
the thalamus, the information is relayed to the appropriate part of the cerebral cortex. (Fig.
20.1)
Sensory organs consist of the specialised perceptional elements of ectodermal origin, and
accessory supporting or protective structures mostly of mesenchymal origin.
Sensory input
Areas of forebrain
primary
visual
cortex
eyes
ears
midbrain
thalamus
temporal
lobe
skin
primary
sensory
cortex
taste
medulla
oblongata
olfactory
bulb
smell
limbic system
and olfactory
cortex
Figure 20.1 Impulses transmission from the sensory organs into the competent portions
of the CNS.
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20.1. Development of eye and related structures
Early eye development results from a series of inductive signals. The eyes are derived from
four sources:
1) the neuroectoderm of the forebrain
2) the surface ectoderm of the head
3) the mesoderm between the neuroectoderm and surface ectoderm
4) the neural crest cells
The neuroectoderm differentiates into the retina, the posterior layer of iris and epithelial
layer of corpus ciliare, and the optic nerve. The surface ectoderm gives rise to the primordia
of lenses. The mesoderm between the neuroectoderm and surface ectoderm gives rise to
mesenchyme from which the fibrous and vascular coats (sclera and choroidea) of the eye
develop. Neural crest cells migrate into the mesenchyme and contribute to the sclera, part of
the cornea, choroid, ciliary body and iris, and blood vessels of the eye.
The area of the neural plate that gives rise to the eyes primordia is initially a single medial
region near the anterior margin of the prosencephalon, the optic field. At the end of the third
week of gestation in most species, shallow grooves are formed on the sides of forebrain. (Fig.
20.2) With closure of the neural tube these grooves expand as outpockets of the
prosencephalon – the optic vesicles. The optic vesicles cavities are initially continuous with
the cavity of the forebrain and they remain connected with the prosencephalon by the optic
stalk.
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The optic vesicles grow laterally until their lateral wall comes into contact with the surface
ectoderm. The neuroepithelium of the optic vesicles induces the surface ectodermal
epithelium to proliferate and form the lens placodes. The lens placodes subsequently
invaginate, forming lens pits and then spherical lens vesicles, which lose the contact with the
surface ectoderm. As the lens vesicles develop, the optic vesicles invaginate and become
double-layered optic cups. The inner and outer layers of the optic cup are at first separated
by a lumen, the internal space, but it soon disappears, and the two layers appose each other.
The outer layer of the optic cup becomes the pigmented layer of the retina. The inner layer of
the optic cup differentiates into the neural retina with three layers of neurons ensuring visual
perception.
Linear grooves, choroid or optic fissures, develop on the ventral surface of the optic cups
and along the optic stalks. (Fig. 20.3) The centre of the optic cup, where the retinal fissure is
deepest, forms the optic disk. The developing axons of the retinal ganglion layer cells pass
directly into the optic stalk and convert it into the optic nerve. The myelination of nerve fibers
begins during the later period of foetal development and during the first postnatal year.
Figure 20.3 The closure of the choroid fissure in the optic stalk, incorporation of the
hyaloid vessels into the optic stalk and subsequent formation of the optic nerve.
A – ventral view of the optic cup, B cross section of the optic stalk. 1 – lens, 2 – choroid
fissure, 2a – closed choroid fissure, 3 – optic stalk, 3a – nervus opticus, 4 – lumen of optic
vesicle, 5 – inner layer of the optic stalk, 5a – axons of the nervus opticus, 6 – outer layer of
the optic stalk, 7 – mesenchyme, 8 – central retinal artery and vein, 9 – pia mater Modified
from Sinowatz and Rűsse (2007).
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The fissures contain vascular mesenchyme from which the hyaloid blood vessels develop.
The hyaloid artery supplies the inner layer of the optic cup, the lens vesicle and the
mesenchyme in the cavity of the optic cup, and the hyaloid vein returns the blood back. (Fig.
20.3) As the edges of the retinal fissure fuse, the hyaloid vessels are enclosed within the
primordial optic nerve. Distal parts of the hyaloid artery usually degenerate, but proximal
parts persist as the central artery and vein of retina.
During the optic cup formation the forebrain (prosencephalon) differentiates to two parts, the
telencephalon and diencephalon, and the optic stalk insertion shifts to the diencephalon
region.
20.1.1. Development of the retina
The retina develops from the apposed walls of the optic cup, which initially are separated by
the intra-retinal space. The outer, thinner wall of the optic cup remains thin and becomes
pigmented, and gives rise to the pigmented layer of the retina. Moreover it contributes to the
formation of the ciliary body and iris. The inner, thicker wall of the optic cup differentiates
into the neural retina. But an outer region near the rim of the optic cup remains thin-walled
and presents blind area of the retina (pars caeca retinae). Subsequently it also contributes to
the formation of the ciliary body and iris.
The neural retina cells differentiate and proliferate in a manner analogous to the stages of
neural tube differentiation, forming multi-layered structure. The sensory pathway of the retina
consists of a chain of three neurons. The first in the chain are the light-sensitive cells, rods
and cones. They synapse with processes of the bipolar neurons. The efferent process of each
bipolar neuron establishes synapse with the third neuron in the chain, the ganglion cell. Long
axons of ganglion cells course towards the optic disc (nerve fibers layer of the retina)
through which they leave the eyeball and enter the optic stalk. In the optic stalk the axons
form the optic nerve by which the signals are related to the visual cortex of the brain.
Another important cell types which differentiates within the inner wall of the optic cup are the
Müller glial cell, amacrine cells and horizontal cells. Müller glial cells provide mechanical
support and nutrition to the retina, a role analogous to that of the fibrous astrocytes in the
central nervous system. Amacrine and horizontal cells are involved in the horizontal
distribution of the signals.
The cellular layers constituting the inner wall of the optic cup are designated according to
their positions relative to the outer wall. Accordingly, the cells of the inner wall which are
adjacent to the pigmented retinal layer are called the outer visual layer of the retina, and the
retinal layer more distant from the pigmented layer is referred to as the inner layer. Thus, light
passes through the inner layers of the retina before reaching the visual receptors. The
vertebrate retina is named inverted retina.
The normal development and differentiation of the neural retina is a complicated system of
interaction which depends upon its contact and interaction with the pigmented layer, as well
as interactions between the neural and glial elements within the neural layers. Disorders of
these contacts result in abnormal development of the retina.
In ungulates, retinal differentiation and maturation is essentially completed at birth whereas in
carnivores they continue for up to 5 weeks after birth.
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Figure 20.4 Development of the retina and associated structures of the eye.
1 – mesenchyme, 2 – ectoderm, 3 – future anterior chamber, 4 – developing lens, 5 – outer
layer of the optic vesicle, future pigmented retinal layer, 6 – inner layer of the optic cup,
future neural retinal layer, 7 – lumen of the optic cup, 7a - intraretinal space, 8 – hyaloid
artery, 9 – eyelid, 10 – cornea, 11 – future anterior chamber, 12 – sclera, 13 – anterior lens
epithelium, 14 – iris, 15 – anterior chamber, 16 – conjunctival sac, 17 – ciliary body, 18 –
choroid with blood vessels, 19 – posterior chamber, 20 – vitreous body, 21 – optic nerve, 22 –
elastic lens capsule, 23 – suspensory ligament of lens, 24 – hyaloid canal, 25 – central artery
of retina, 26 – pigmented retinal layer, 27 – neural retinal layer
20.1.2. Lens
Where the optic vesicles come to contact with the surface ectoderm, the ectoderm thickens to
form the lens placodes. These structures subsequently invaginate and form lens pits and
subsequently lens vesicles, which break away from the surface ectoderm. (Fig. 20. 5 A-D)
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At this stage the lens vesicle merely consists of a single layer of epithelial cells. The cells of
posterior wall of the vesicle start to elongate and form primary lens fibers, which fill the
vesicle cavity and thereby transform it into a solid lens. (Fig. 20.5 E) During the next growth
of the lens, further, secondary lens fibers are continuously added to the central lens core.
They are formed by less differentiated cells located at the lens equator, which proliferate,
move to the posterior pole and serve as a source for the new (secondary) lens fibres.
The anterior lens surface is covered by a single layer of cuboidal cells which retain their
nuclei, and merges with proliferative cells at the equatorial margin of the lens.
The cells of the lens secrete a basal membrane like, elastic matter rich in glycoproteins that
covers the surface of the lens and forms the lens capsule. (Fig. 20.5 C) This lens capsule
contributes to the elastic properties of the lens, essential to its function. The suspensory
ligaments of the lens, zonular fibers, develop from the surrounding mesenchyme. These
radial collagenous fibres situated between the ciliary body and the lens are attached to the lens
capsule at point of meridian.
During cell differentiation in the lens, all cell organelles gradually disappear, the lens fibers
become anucleate, with only inner cytoskeleton and transparent cytoplasm filled with proteins
called crystallins. The crystalline proteins appear in a characteristic sequence: first αcrystalline proteins, then, when the cells elongate, ß-crystallins and finally, only in the
terminally differentiated lens fibres, γ-crystallins.
The development of the lens is strongly influenced by the retina. Fibroblast growth factor
secreted by the retina accumulates in the vitreous humour behind the lens and stimulates the
formation of the lens fibers.
20.1.3. Vitreous body
The vitreous body develops from mesenchyme, which penetrates into the optic cup cavity by
way of the choroid fissure. The interstitial spaces of this loose fibrillar mesh fill with
transparent gelatinous substance. During much of embryonic development the hyaloid artery
supplies the vitreous body. Later the vitreous part of the hyaloid artery regresses, leaving the
hyaloid canal in the vitreous body.
20.1.4. Cornea
The development of the cornea is induced by the lens vesicle. Its inductive influence results in
transformation of the surface ectoderm into the transparent, multi-layered avascular cornea.
The cornea is formed from three sources:
1) the external corneal epithelium is derived from the surface ectoderm
2) stroma of the cornea is derived from the mesenchyme
3) the internal corneal epithelium differentiates from the neural crest cells
20.1.5. Choroid and sclera
The mesenchyme surrounding the optic cup (largely of neural crest origin) differentiates
under the inducting influence of the retina into an inner vascular layer, the choroid, and an
outer fibrous layer, the sclera. Towards the rim of the optic cup, the choroid becomes
modified to form the cores of the ciliary processes; the sclera becomes continuous with the
stroma of the cornea.
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Figure 20.5 Development of the lens. 1 – ectoderm, 2 – lens placode, 3 - lens pit, 4 – lens
vesicle, 5 – posterior wall of the lens vesicle, primary lens fibers, 6 – anterior lens epithelium,
7 – developing lens after obliteration of the cavity, 8 – lens capsule
20.1.6. Ciliary body
The ciliary body (corpus ciliare) stroma develops from the mesenchyme. The ciliary
epithelium represents the anterior prolongation of the peripheral portion of the optic cup
(neuroectoderm). The ciliary muscle develops from the mesenchyme. (Fig. 20.6)
20.1.7. Iris
The iris, likewise the ciliary body, develops partially from the peripheral portion of the optic
cup. The posterior epithelium of iris consists of an inner non-pigmented epithelial layer and
an outer pigmented layer, which are continuous with the neural and pigmented layers of the
retina, respectively. The connective tissue (stroma) of the iris is derived from the neural crest
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cells that migrate into the iris. (Fig. 20.6) The muscles of the iris (m. sphincter and m.
dilatator pupillae) are derived from the neuroectoderm of the optic cup. They appear to arise
from the anterior epithelial cells of the iris by transformation of the epithelial cells.
Figure 20.6 Development of the iris and ciliary body. Modified from McGeady et al.
(2006).
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20.1.8. Chambers of the eye
Initially, slits in the mesenchyme between the iris and the cornea develop and fuse, forming
the anterior chamber. Marginal layer of this mesenchyme becomes flattened and gives rise to
the endothelium, which attaches to the posterior side of the cornea and anterior side of the iris.
The posterior chamber develops in the same manner by fusion of slits in the mesenchyme
between the posterior side of the iris and the anterior side of the lens. The chamber fluid
produced by the ciliary body subsequently fills the eye chambers. In birds the chamber fluid is
produced also by the pecten.
The pecten or pecten oculi is a comb-like structure belonging to the choroid in the eye of all
birds and some reptiles. It is a non-sensory, vascularised, pigmented structure that projects
into the vitreous body from the point where the optic nerve enters the eyeball. The pecten is
believed to both nourish the retina and control the pH of the vitreous body.
20.1.9. Accessory organs of the eye – eyelids, lacrimal gland and ophtalmogyric muscles
The eyelids develop from two cutaneous folds of ectoderm with mesenchymal core that grow
over the cornea. They grow rapidly towards each other until they meet and fuse with one
another. This temporary fusion involves only the epithelial layer of the eyelid. Separation of
the eyelids occurs before birth in humans, horses, pigs and ruminants and after birth in
carnivores.
The eyelashes and glands in the eyelids (the tarsal glands) are derived from the surface
ectoderm and they begin to differentiate before the eyes reopen. In dogs no eyelashes develop
in the lower eyelids.
The thin mucous membrane covering the inner surface of the eyelid continuing over the
anterior surface of the sclera is called conjunctiva. The space between the eyelid and the
anterior surface of the eyeball is known as the conjunctival sac. In domestic animals, a fold
of mesenchyme covered by conjunctiva develops and protrudes into the conjunctival sac,
forming the third eyelid. Later, from the underlying mesenchyme differentiates the cartilage
plate that gives rigidity to the third eyelid.
The lacrimal gland develops from a number of solid buds from the surface ectoderm at the
dorsolateral angle of the orbit, which dip into the mesenchyme of circumbulbar Tenon´s
space.
The ophtalmogyric muscles (mm. recti bulbi, mm. obliqui bulbi, m. retractor bulbi) are
derived from mesenchyme in the second pharyngeal arch and are supplied by oculomotor
(III.), trochlear (IV.), and abducent (VI.) head nerves.
20.2. Development of the ear
The ear is composed of three anatomic compartments, the outer, middle and inner ear, each
of different embryonic origin. The structures of the outer and middle ear are derived from the
first and second pharyngeal arches and the intervening first pharyngeal pouch and cleft. The
inner ear develops from the thickened surface ectoderm – ectodermal placode at the level of
the hindbrain.
The outer ear consists of the auricle, external auditory meatus (meatus acusticus externus)
and the external layer of the tympanic membrane (membrana tympani).
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The middle ear is formed by tympanic or middle ear cavity (cavum tympani) and auditory
tube (tuba auditiva, Eustachian tube). Transport of sound waves from the external to the inner
ear is ensured through a chain of three middle ear ossicles (ear bones - malleus, incus, and
stapes) which are located within the middle ear cavity and connect the inner side of the
tympanic membrane to the oval window of the middle ear. Other component of middle ear are
muscles, musculus tensor tympani and musculus stapedius.
The inner ear consists of the membranous labyrinth with vestibulocochlear organ and
associated ganglia. The sensory apparatus is involved in both hearing and balance. The inner
ear is surrounded by the cartilaginous otic capsule, which later ossifies.
20.2.1. Development of the inner ear
The primordia of the inner ear are otic placodes, bilateral thickenings of the surface
ectoderm, which develop in a position lateral to the myelencephalon. Inductive signals from
the paraxial mesoderm and notochord stimulate the surface ectoderm to form them. Each otic
placode invaginates to form the otic pit. After a short time, the lips of the pit close, separating
the otic vesicle, the primordium of the membranous labyrinth, from the surface ectoderm. The
cavity of the otic vesicle fills with a fluid called endolymph. Some cells that break away from
the ventromedial wall of the otic vesicle later give rise to the sensory ganglion (ganglion
statoacusticum) of the vestibulocochlear nerve (VIII).
The finger-like diverticulum evaginates from the dorsomedial region of the otic vesicle and
elongates to form the endolymphatic duct. The terminal portion of this duct dilates forming
the endolymphatic sac which occupies a position beneath the dura mater. The otic vesicle
differentiates into two distinct regions, a dorsal expanded part referred to as the utricle
(utriculus), and a ventral portion, the saccule (sacculus).
Two flat, disc-like diverticula grow from the utricle. One of these structures occupies a
vertical position parallel to the median plane. The second is positioned at right angle to the
first, horizontally and laterally. Division of the vertical diverticulum gives rise to the anterior
and posterior semicircular structures. Subsequently, the central portions of these discshaped structures vanish due to apoptosis and the two tubes remaining are termed the
anterior and posterior semicircular ducts that later become orientated at 90° to each other.
Similarly, the central area of the horizontal diverticulum undergoes apoptosis, leaving residual
structure, the lateral semicircular duct. One end of each semicircular duct enlarges at its
junction with the utriculus, forming an ampulla. In the ampullae, specialised structures
formed by receptor cells develop – the cristae ampullares. Together with analogic
specialised compartments of the utricle and saccule epithelium, the macula utriculi and
macula sacculi, they represent the sensory organ of balance.
From the ventral part of the saccule the tubular cochlear duct evaginates, grows and coils to
form the membranous cochlea. The connection of the cochlea with the saccule becomes
constricted and forms the narrow ductus reuniens. (Fig. 20. 7)
The spiral organ (of Corti) differentiates from the cells in the wall of the cochlear duct.
Ganglion cells of the vestibulocochlear nerve (VIII) migrate along the coils of the
membranous cochlea and form the spiral ganglion of cochlea. The cells of the spiral ganglion
retain their original embryonic bipolar appearance. Their axons extend from this ganglion to
the spiral organ, where they terminate on the hair cells.
Under the inductive influence of the otic vesicle the surrounding mesenchyme condenses and
forms the cartilaginous otic capsule. The inner lining of the cartilaginous capsule undergoes
apoptosis, leaving a perilymphatic space between the membranous labyrinth and the
cartilage. This space becomes filled with fluid, the perilymph. In consequence of reshaping
and enlarging of the cochlear duct, the perilymphatic space is divided into two divisions,
219
scala vestibuli and scala tympani, (Fig. 20.8) which are separated from one another, except
at the apical tip. An opening at the apex of the cochlea that connects the scala vestibuli and
scala tympani is called helicotrema.
The cartilaginous otic capsule later ossifies to form the bony labyrinth of the internal ear.
Figure 20.7 Development of the otic vesicle into the membranous labyrinth of the inner
ear. 1 – endolymphatic duct, 2 – utricular part of the otic vesicle, 3 – saccular part of the otic
vesicle, 4 – developing posterior semicircular duct, 5 – developing anterior semicircular duct,
6 – absorption area, 7 – lateral semicircular duct, 8 – saccule, 9 – developing cochlear duct, 10
– saccus endolymphaticus, 11 – semicircular ducts, 12 – ampullae, 13 – utricle, 14 – ductus
reuniens, 15 – membranous cochlear duct. Modified from Moore et al. (2013).
220
The inner ear development in birds is similar to that of mammals. The cochlear duct, named lagena in
birds, is shorter, blind-ending and usually straight. The lagena is filled with endolymph and from the
perilymphatic duct is separated by a basilar membrane. Corti organ cells are accumulated only to a
small basilar papilla. Likewise in mammals, several specialised cells develop within originally
homogenous population of unspecialised columnar cells. (hair, pillar, phalangeal, etc.) The hair cells,
primary auditory cells of Corti organ, lying on the inner, neural side differ from that on the outer,
abneural side. They are described as tall hair cells (THS) (neural side) and short hair cells
(SHC)(abneural side) and it was discovered, that while the tall hair cells are very similar in function
to that of the inner hair cells of mammals, many of short hair cells have no afferent nerve contact with
brain.
Figure 20.8 Successive stages of development of the spiral organ and the perilymphatic
space.
221
20.2.2. Development of the middle ear
The tympanic cavity and auditory tube (Eustachian tube) develop from the first pharyngeal
pouch, the endodermal evagination of the foregut between the first and second pharyngeal
arches (see Chapter 13). (Fig. 13.12) Due to both these structures are lined with an endodermderived epithelium. Common base of the middle ear, named tubo-tympanic recess, later
differentiates; its dorsal part gives rise to the tympanic cavity and ventral part to the auditory
tube. (Fig. 20.9) In the Equidae, a ventral diverticulum develops from each auditory tube and
gives rise to the large mucus-secreting sac, the guttural pouch.
The blind end of the first pharyngeal pouch approaches the innermost portion of the first
pharyngeal cleft. Between the endodermal epithelium of the pharyngeal pouch and the
ectodermal lining of the pharyngeal cleft remains the layer of mesenchyme. This three-layered
partition is called membrana obturans. Later, the thickness of the mesenchymal layer
decreases significantly and whole complex, consisting of tissues originating from all three
germ layers, establishes the tympanic membrane (eardrum, membrana tympani).
Middle ear ossicles are formed from the neural crest-derived mesenchyme of the first and
second pharyngeal arches. The malleus and incus are formed from the mesenchyme of the
first pharyngeal arch while the stapes originates from the mesenchyme of the second
pharyngeal arch. Later, the mesenchyme of the ossicles becomes cartilaginous and finally the
cartilage is replaced by bone. The surrounding loose mesenchymal tissue is resorbed and the
ossicles become suspended in air-filled cavity. The endodermal epithelium which lines the
tympanic cavity extends into the newly formed cavity, where surrounds and also suspends the
ossicles. The malleus, which becomes anchored to the tympanic membrane, articulates with
the incus, which in turn articulates with the stapes. The oval-shaped footplate of the stapes fits
into a corresponding oval opening in the osseous labyrinth, the vestibular window, where it is
held in position by a flexible annular ligament.
The muscles, which assist in the transmission of auditory stimuli, develop from the first
pharyngeal arch (m. tensor tympani) and from the second pharyngeal arch (m. stapedius). The
tensor tympani muscle is innervated by the cranial nerve V (trigeminal nerve), and the
stapedius muscle is innervated by the cranial nerve VII (facial nerve).
20.2.3. Development of the external ear
The external auditory meatus develops from the first pharyngeal cleft. Epithelial cells at the
blind end of this invagination proliferate, forming the solid epithelial mass, the meatal plug.
Later in the foetal period, the central cells degenerate and a channel, external auditory
meatus, develops. (Fig. 20.9 C, D) Hair follicles, sebaceous glands and modified sweat
glands, which are responsible for cerumen production, develop from the epithelial buds in the
outer portion of the external canal.
Tympanic membrane (eardrum), as has been described above, contains tissue of three
different origins. It consists of outer ectodermal lining at the bottom of the auditory meatus,
inner endodermal lining of the tympanic cavity and intermediate mesenchyme of the first and
second pharyngeal arches, which give rise to collagen fibers network – fibrous stratum of the
tympanic membrane. The tympanic membrane is firmly fasten to the handle of the malleus
and separates the external auditory meatus from the tympanic cavity.
The auricle (pinna) is formed from mesenchymal tissue of the first and second pharyngeal
arches, auricular hillocks, surrounding the first pharyngeal cleft. Nodular masses of
mesenchyme (6 auricular hillocks) enlarge asymmetrically in a species-specific manner and
222
ultimately fuse to form the auricle which shifts from the base of the neck to its definitive
location.
Innervation of the part of auricle derived from the first pharyngeal arch is ensured with its
nerve, the mandibular branch of the trigeminal nerve; the parts derived from the second
pharyngeal arch are supplied by cutaneous branches of the occipital and auricular nerves.
1
5
10
8
2
3
4
9
6
11
7
12
A
B
15 16 17
22
18
23
24
19
8
21
13
25
14
19
26
C
20
D
Figure 20.9 Development of the external and middle ear.
1 – otic vesicle, 2 – surface ectoderm, 3 – first pharyngeal groove, 4 – membrana obturans,
5 – myelencephalon, 6 – first pharyngeal pouch, 7 – primordial pharynx, 8 – separated otic
vesicle, 9 – derivatives of the first pharyngeal arch cartilage (primordia of malleus and incus),
10 – derivative of the second pharyngeal arch (primordium of incus), 11 – tubotympanic
recess, 12 – second pharyngeal arch, 13 – developing external auditory meatus, 14 – meatal
plug, 15 – malleus, 16 – incus, 17 – stapes, 18 – cartilaginous otic capsule, 19 – tympanic
cavity, 20 – pharyngotympanic tube, 21 – external auditory meatus, 22 – squamous temporal
bone, 23 – perilymphatic space, 24 – membranous labyrinth, 25 – tympanic membrane,
26 – petrous temporal bone. Modified from Moore et al. (2013).
223
20
21 COELOM
The term coelom is used to describe a fluid-filled, mesodermally lined body cavity or spaces.
Placental vertebrate development have both extraembryonic (outside the embryo) and
intraembryonic (inside the embryo) coeloms. The extraembryonic coelom (exocoelom)
includes the yolk sac, amniotic cavity and the chorionic cavity. The intraembryonic coelom
is the single primitive cavity that lies within the mesoderm layer.
At the end of gastrulation the embryonic mesoderm consists of three regions, paraxial,
intermediate and lateral mesoderm. As development proceeds, clefts develop in the right and
left lateral mesoderm. Later these clefts fuse forming a cavity which splits the lateral
mesoderm into an outer layer of somatic mesoderm and inner layer of splanchnic
mesoderm. (Fig 5.7)
The cavities between the two layers of lateral mesoderm located on either side of the midline
are referred to as coelomic cavities. They extend cranially, meet and fuse in front of the
developing neural and cardiogenic plates, forming horse-shaped coelomic cavity. The lateral
walls of the coelomic cavity are composed of somatic mesoderm which fuses with ectoderm
forming somatopleura. The medial walls are composed of splanchnic mesoderm which fuses
with endoderm forming splanchnopleure. The mesodermal cells lining the coelomic cavity
differentiate into a simple squamous epithelium, referred to as mesothelium. In consequence
of cranial, caudal and lateral folding of the embryo, the cranial region of the horse-shaped
coelom occupies a position ventral to the foregut and the developing heart, and gives rise to
the primordium of the pericardial cavity. The right and left limbs of the coelomic cavity are
connected to the pericardial cavity by the pericardial-peritoneal canals. (Fig. 21.1)
Figure 21.1 Formation of the pericardial and peritoneal cavities and the pericardialperitoneal canals (left lateral view). Modified from McGeady et al. (2006).
224
Lateral body folding results in division of the developing embryonic coelom into intraembryonic and extra-embryonic regions, which communicate initially through coelomic
portals at the umbilicus. Subsequently become separated from each other.
The extra-embryonic coelom is associated with the developing foetal membranes.
The intra-embryonic coelom will be later partitioned into the 3 major body cavities,
pericardial, pleural, and peritoneal, by the diaphragm, pleuroperitoneal membranes and
by the pleuropericardial folds between the heart and lungs.
21.1. Mesenteries
Developing organs push against an internal wall of the coelom cavity, generating a coat
surrounding organs, which is formed by epithelium and associated layer of underlying loose
connective tissue. The duplicature of splanchnopleure dorsally and ventrally from the
primitive gut creates the base of mesentery, which connects the organs to the body wall and
conveys the nerves and blood vessels. Temporarily, the dorsal and ventral mesenteries divide
the peritoneal cavity into right and left halves, but the ventral mesentery soon disappears,
except to the primordium of stomach and duodenum. Thus the peritoneal cavity becomes a
continuous space.
21.2. Development of the body cavities
The first cavities appear inside non-segmented head mesoderm, forming the paired
primordium of the horseshoe-shaped pericardial cavity. Later, due to folding of the embryo,
the pericardial cavity shifts caudoventrally and after the mesocardium disappears, both
cavities become continuous. Dorsally, above the pericardial cavity, the primordium of the
pleural cavity is created, separated by the mediastinum to two halves. Initially, both these
cavities communicate. (Fig. 21.2)
Caudally, next two cavities in the general mesoderm form and unite on the ventral aspect of
the gut, forming the primordium of the peritoneal cavity, which becomes continuous with the
remains of the extra-embryonic coelom around the umbilicus. The peritoneal cavity is
interconnected with pleural cavity by pleuro-peritoneal canals. (Fig. 21.3) Its dorsal part is
partitioned by the dorsal mediastinum. Thus the integral body cavity, called pleuropericardo-peritoneal cavity, is established.
To the partition of the pleuro-pericardo-peritoneal cavity to definitive parts contribute three
following structures: septum transversum, membrana pleuropericardiaca and plicae
pleuroperitoneales.
Septum transversum is the mass of mesenchyme between the stomach and the ventral body
wall, in which sinus venosus, ductus Cuvieri and venae omphalomesentericae are involved.
This mass of mesenchyme extends across the body of the embryo. Initially, it is attached
ventrally to the body wall between the pericardium and umbilicus; later this partition
separates the heart from the liver primordium and nearly interrupts communication of the
pericardial and peritoneal cavity. In the middle line the septum is perforated by the foregut.
As development proceeds, the dorsal end of the septum transversum is carried gradually
caudalward, and when it reaches the fifth cervical segment, muscular tissue with the phrenic
nerve grows into it. It continues to recede, however, until it reaches the position of the adult
diaphragm at the level of the first lumbar vertebrae. Dorsally the septum transversum does not
reach the dorsal body-wall, leaving the pleuro-peritoneal canals opened. The liver buds grow
into the septum transversum and undergo development there. Originally wide connection with
225
the liver primordium becomes narrower and later gives rise to the ligaments, which connect
the liver to diaphragm (triangular, falciform and coronary ligaments).
Figure 21.2 Separation of the pleural and peritoneal cavities. Arrows indicate extension
of the pleural cavity into the body wall. Cross section through thoracic region. Modified from
McGeady et al. (2006).
226
The ultimate separation of the pleuro-peritoneal cavity from one another is effected by the
growth of a ridge of tissue, so called pulmonary ridge, on either side from the mesoderm
surrounding the duct of Cuvier. The front part of this ridge grows across and obliterates the
pleuro-pericardial opening. Finally the pulmonary ridges grow together, forming pleuropericardial membrane (membrana pleuropericardiaca). (Fig. 21.2 B, C)
With the continued growth of the lungs the pleural cavities and membrana pleuropericardiaca
are pushed down in the body wall towards the ventral median line, thus separating the
pericardium from the lateral thoracic walls. Ventrally, the pleuro-pericardial membranes fuse,
forming the fibrous layer, which anchors the pericardium either to the developing diaphragm
or to the ventral thoracic wall, depending on species, and encloses the left and right phrenic
nerves. (Fig. 21.2 D)
The pulmonary ridges continue caudally by way of pleuro-peritoneal folds (plicae
pleuroperitoneales), which develop from the lateral body wall and reach the cranial end of
mesonephros at their dorsal end. The plicae pleuroperitoneales extend medially, fusing
dorsally with the mesothelial fold suspending the oesophagus (mesoesophageum) and
ventrally with the septum transversum. (Fig. 21.3) The partition formed by this fusion
constitutes the primordial diaphragm, which completely separates the pleural cavity from the
peritoneal cavity. The separation of pleural and peritoneal cavities is typical for mammals,
while in reptiles and some birds they continue to be connected.
21.3. Diaphragm
To the diaphragm development contributes mainly septum transversum. Lateral parts of the
diaphragm originate from the pleuro-peritoneal folds. Medial part of the dorsal portion of
the diaphragm develops from the mesenchyme of dorsal mesentery and striated muscles
originate from the myotomes of cervical somites. (Fig. 21.3) Thus the musculature of the
diaphragm is innervated by ventral branches of caudal cervical nerves which form the left and
right phrenic nerves. Ventral branches of thoracic and lumbar spinal nerves innervate the
muscular rim of the diaphragm. Initially, muscles are present within all range of diaphragm;
later, muscles in the central portion of diaphragm are replaced by dense irregular connective
tissue that forms the centrum tendineum.
The diaphragm is pierced by a series of apertures to permit the passage of structures between
the thorax and abdomen. Three large openings — the aortic, the oesophageal, and the vena
cava are described.
227
Figure 21.3 Stages in the development of the diaphragm.¨ Modified from McGeady et al.
(2006).
228
CONTENS:
1 INTRODUCTION
3
2 GAMETOGENESIS
4
2.1. Spermatogenesis
4
2.2. Oogenesis
7
3 SEXUAL MATURITY AND SEXUAL CYCLE
9
3.1. The phases of the oestrous cycle
9
4 FERTILIZATION
12
4.1. Transport of gametes
12
4.2. Phases of fertilization
13
4.3. Fertilization disorders (ectopic pregnancy)
16
4.4. Fertilization in birds
16
4.5. Sex determination
17
5 BLASTOGENESIS
18
5.1. Blastogenesis in mammals
20
5.1.1. Cleavage and blastulation
20
5.1.2. Gastrulation and notogenesis in mammals
22
5.1.2.1. Formation of germ layers
22
5.1.2.2. Primitive streak
22
5.1.2.3. Notochordal process and notochord
24
5.1.2.4. Formation of chorda dorsalis
24
5.1.2.5. Neurulation – formation of the neural tube
29
5.1.2.6. Neural crest formation
30
5.1.2.7. Mesoderm formation
32
5.1.2.8. Development of somites
32
5.2. Blastogenesis in birds
34
5.2.1. Cleavage and blastulation in birds
34
5.2.2. Gastrulation and notogenesis in birds
34
229
6 FETAL MEMBRANES AND EXTRAEMBRYONIC ORGANS
37
6.1. Fetal membranes and extraembryonic organs in mammals
37
6.1.1. Yolk sac (saccus vitellinus)
37
6.1.2. Amnion and chorion
39
6.1.3. Allantois
42
6.2. Fetal membranes in birds
45
6.2.1. The yolk sac development
45
6.2.2. Amnion and chorion
46
6.2.3. Allantois
46
7 IMPLANTATION OF THE GERM
48
8 PLACENTA AND TYPES OF PLACENTA
50
9 EMBRYO SHAPE DEVELOPMENT
57
9.1. Development of the face
62
9.2. Pharyngeal or branchial pouches
63
9.3. Pharyngeal arches
63
9.4. Pharyngeal grooves
63
10 THE SKELETAL SYSTEM
68
10.1. Intramembranous (desmogenous) ossification
68
10.2. Endochondral ossification
69
10.3. Development of the bone joints
73
10.4. Axial skeleton development
75
10.4.1. The development of vertebral column
75
10.4.2. Development of the ribs and sternum
77
10.4.3. Development of the cranium
77
10.5. Development of limb bones
80
10.6. Development of avian skeleton
81
11 MUSCULAR SYSTEM
82
11.1. Smooth muscle development
82
11.2. Striated muscle development
82
230
12 DEVELOPMENT OF THE BLOOD CELLS, VASCULAR SYSTEM
AND HEART
85
12.1. Formation of blood cells (haemopoiesis)
86
12.2. Heart
86
12.3. Segmentation of the cardiac tube and the curvature formation
89
12.4. Septation of the heart and formation of the heart chambers
90
12.4.1. Incorporation of the sinus venosus into the atrium
90
12.4.2. Septation of the atrioventricular canal - septum intermedium
92
12.4.3. Development of the atrial septum
92
12.4.4. Formation of the ventricular septum
94
12.4.5. Septation of the cono-truncus
94
12.4.6. Development of aortic and pulmonary valves
95
12.4.7. Development of the conducting system of the heart
95
12.5. Development of the arterial system
97
12.5.1. Aortic arches and their derivatives
97
12.5.2. Branches of dorsal aorta
98
12.6. Development of venous system
100
12.6.1. Vitelline veins
100
12.6.2. Umbilical veins
100
12.6.3. Cardinal veins
101
12.7. Blood circuit development
101
12.7.1. Fetal circulation
102
12.7.2. Changes in circulation at birth
102
12.8. Development of lymphatic vessels and lymph nodes
104
12.9. Development of haemolyphonoduli
105
12.10. Development of spleen
105
13 DIGESTIVE SYSTEM
107
13.1. Primary oral and nasal cavities
107
13.2. Craniofacial development
110
13.3. Palate
110
13.4. Oral cavity
113
13.5. Teeth
113
13.6. Salivary glands
118
231
13.7. Tongue
118
13.8. Thyroid gland
120
13.9. Pharynx and its derivatives
120
13.9.1. Pharyngeal clefts
122
13.9.2. Pharyngeal arches
122
13.9.3. Pharyngeal pouches
122
13.10. Oesophagus
124
13.11. Stomach
125
13.11.1. Simple stomach
125
13.11.2. Compound stomach of ruminants
127
13.12. Liver
129
13.13. Pancreas
130
13.14. Intestine
132
13.15. Gastrointestinal tract of birds
135
14 RESPIRATORY SYSTEM
136
14.1. Nasal cavity
136
14.2. Larynx
137
14.3. Trachea
138
14.4. Bronchi and lungs
138
14.5. Avian lungs
141
15 URINARY SYSTEM
142
15.1. Kidney
142
15.1.1. Pronephros
142
15.1.2. Mesonephros
144
15.1.3. Metanephros
144
15.1.4. Unilobar kidneys
147
15.1.5. Multilobar kidneys
147
15.2. Urinary bladder
149
16 REPRODUCTIVE SYSTEM
151
16.1. Development of the male and female genital organs
16.1.1. Undifferentiated stage
151
151
232
16.1.2. Differentiated stage – differentiation and maturation of testes
16.1.2.1. Descent of the testes
16.1.3. Differentiated stage – differentiation and maturation of ovaries
16.1.3.1. Descent of the ovaries
153
153
156
156
16.2. Development of the sexual duct system
158
16.2.1. Undifferentiated stage
158
16.2.2. Differentiated stage – male sexual duct system
158
16.2.3. Differentiated stage – female sexual duct system
159
16.3. Development of the external genitalia
162
16.3.1. Undifferentiated stage
162
16.3.2. Differentiated stage - formation of male external genital organs
163
16.3.3. Differentiated stage - formation of female external genital organs 164
16.4. Urogenital system of birds
165
17 ENDOCRINE SYSTEM
167
17.1. Pituitary gland
167
17.2. Pineal gland
169
17.3. Adrenal gland
169
17.4. Thyroid gland
171
17.5. Parathyroid gland
171
17.6. Pancreatic islets
171
18 INTEGUMENTARY SYSTEM
173
18.1. Epidermis
173
18.2. Dermis (corium)
175
18.3. Hypodermis (subcutis)
175
18.4. Epidermal appendages
175
18.4.1. Hair
175
18.4.2. Sinus hair (sensory or tactile hair)
178
18.4.3. Hair growth cycle
178
18.4.4. Skin glands
179
18.4.4.1. Sebaceous glands
179
18.4.4.2. Sweat glands
180
18.4.5. Development of the mammary gland
233
180
18.4.5.1. Development of the bovine mammary gland
18.4.6. Hooves and claws
181
182
18.4.6.1. Equine hoof
183
18.4.6.2. Ruminant and porcine hooves
184
18.4.6.3. Canine and feline claws
184
18.4.7. Horns
186
19 NERVOUS SYSTEM
187
19.1. Neurulation
187
19.2. Neural crest
189
19.3. Neural tube
191
19.4. Development of the spinal cord
193
19.5. Development of the brain
195
19.5.1. Rhombencephalon (hindbrain)
195
19.5.2. Myelencephalon
195
19.5.3. Metencephalon
198
19.5.3.1. Cerebellum
198
19.5.4. Mesencephalon
199
19.5.5. Prosencephalon (forebrain)
199
19.5.6. Diencephalon
200
19.5.7. Telencephalon
200
19.6. Meninges
203
19.7. Development of the peripheral nervous system
205
19.7.1. Spinal nerves
206
19.7.2. Cranial nerves
206
19.7.2.1. Special sensory nerves
206
19.7.2.2. Mixed nerves of pharyngeal arches
207
19.7.2.3. Somatic efferent cranial nerves with motor function
207
19.7.3. Autonomic nervous system
207
19.7.3.1. Sympathetic nervous system
207
19.7.3.2. Parasympathetic nervous system
208
19.7.3.3. Enteric nervous system
208
234
20 SENSORY SYSTEM
210
20.1. Development of eye and related structures
211
20.1.1. Development of the retina
213
20.1.2. Lens
214
20.1.3. Vitreous body
215
20.1.4. Cornea
215
20.1.5. Choroid and sclera
215
20.1.6. Ciliary body
216
20.1.7. Iris
216
20.1.8. Chambers of the eye
218
20.1.9. Accessory organs of the eye
218
20.2. Development of the ear
218
20.2.1. Development of the inner ear
219
20.2.2. Development of the middle ear
222
20.2.3. Development of the external ear
222
21 COELOM
224
21.1. Mesenteries
225
21.2. Development of the body cavities
225
21.3. Diaphragm
227
CONTENS
229
INDEX
236
REFERENCES AND FURTHER READING
254
235
INDEX
A
abomasum
accessory sex glands
acetylcholine
acropodium
acrosin
acrosomal phase
acrosomal reaction
acrosome
adamantine membrane
adenohypophyseal
cleft
pouch
vesicle
adenohypophysis
adrenal
cortex
definitive
foetal
gland
medulla
air capillaries
sacs
allantoamnion
allantochorion
allantois
allocortex
alveolar
ducts
sacs
alveoli
amacrine cells
ameloblasts
amnioblasts
amniogenic side
amnion
amniotic cavity
amniotic
fluid
fold
folds
caudal
cranial
lateral
suture
amniota
ampulla
anagen
anal canal
133
folds
162
glands
133
membrane
162
zone
133
39, 85
angioblasts
angiogenesis
39, 85
73, 75
annulus fibrosus
anti-Müllerian hormone (AMH) 158
antrum folliculi
7
aorta
abdominal
97
thoracic
97
aortae
dorsal
88, 97
ventral
88, 89, 97
97
aortic arches
appendix epididymis
158
testis
158
apex cordis
90
apical ectodermal ridge
64, 67, 81
apocrine glands
180
apoptosis
66, 67, 81,
187
apposition
69
arachnoidea
203
arachnoid membrane
204
archenteron
107
arches
aortic
97, 98
pharyngeal
63
vertebral
76
archicortex
202
arcus vertebrae
76
area
opaca
34, 45
pellucida
34, 45
vitellina
34, 45
arrector pilli muscle
175
arteria lienalis
106
arteriae umbilicales
42, 47
arteries
97-100
arytenoid swellings
137
ascending aorta
94, 98
ascending segment
90
astrocyte
192
atresia
156
atrial loop
90
atrioventricular canals
92
atrioventricular node
95
127
158
207, 208
67
13
7
13
7
114
167
167
167
167
169, 170
170
170
169
169, 170
141
141
42
42, 47
37, 42, 46,
107
202
140
140
140, 180
213
114
40
39
37, 39, 45, 46
22, 146, 224
37, 40
39
57
57
57
39
37
159, 219
178
236
atrium
auditory meatus
external
auditory tube
Auerbach´s plexus
auricle
auricular hillocks
autonomic ganglia
nervous system
parasympathetic
sympathetic
autopodium
avian skull
axial skeleton
structures
axonema
axopodium
B
basal nuclei
basal plate
basipodium
bipotent progenitor cells
glial
neuronal
bladder
gall
urinary
blastema
blastocoele
blastocyst
blastoderm
blastodisc
blastogenesis
blastomeres
blastulation
blood islands
blood sinuses
blood-testis barrier
body of vertebra
bone
lamellar
marrow
woven
bony
collar
labyrinth of inner ear
spicules
Bowman´s capsule
brachiocephalic trunk
89-92
122
222
123, 219, 222
208
219, 222
63, 222
205
207
208
207
67
81
75
57
7
67
brain stem
208
branchial arches
63, 97
159
broad ligament
bronchi
dorsobronchi
141
lobar
139
parabronchi
141
principal
138
segmental
140
ventrobronchi
141
138, 141
bronchial buds
tree
140, 141
bronchioles
respiratory
140
terminal
140
broncho-pulmonary segments 140
Brunner´s glands
133
bud
bronchial
138
dental
113, 114
pancreatic
130
bulbourethral gland
158
bulbo-ventricular loop
90
89, 90
bulbus cordis
bulbus olfactorius
200
bundle of His
95
bursa Fabricii
135
bursa omentalis
125
202
77
67
191
191
130
149
69
34
20
35
35
3, 18, 20, 34
18, 20
3, 18, 20
39, 85
178
3
75
C
caecum
calcitonin
calyx
cambium
canalis cervicalis
uterovaginalis
capacitation
caput pancreatis
cardia
cardiac tube
cardiogenic plate
cardiogenic tube
carotid arteries
common
external
internal
cartilage bone models
cartilage Meckel´s
cartilage model
plates
68
72
68
69
220
69
145, 146, 147
98
237
133
120
147
69
63
159
13
130
125
86, 89
24, 86
86, 97
98
98
98
80
122
69
77
Reichert´s
122
cartilages laryngeal
122
118
cartilago dorsi linguae
51
caruncles
catagen
178
193
cauda equina
cavitation
40, 187
cells
alveolar, type I
140
alveolar, type II
140
astrocytes
192
basket
198
C
120, 123
chief
171
endocrine
167
acidophils
167
basophils
167
chromaffin 170
chromophobes 167
G
171
PP
171
α, β, γ
171
epidermal stem
173
follicular
7, 156
glioblasts
192
granule
198
granulosa cell
7
indifferent
153
Langerhans
174
Leydig (interstitial) 153
melanoblasts
173
Merkel
173
mesenchymal stem 68
mesodermal
85
microglial
192
Müller glial
213
myogenic
82
myoid
153
neuroblasts
192, 202
neurons
202
of adenohypophysis 167
of liver
129
of neural crest
189, 205, 211
of neurohypophysis 167
oligodendrocytes
192
oxyphil
171
parafollicular
120, 123
pneumocytes
140
pre-follicular
7
primitive blood
85
primordial germ cells 7
Purkinje
198
radial glial
192, 202
satellite
82, 205
Sertoli
153
spongioblasts
192
stellate
198
151, 153
cellular cords
cementocytes
114
cementum
113, 114
central artery of retina
213
central canal
193
227
centrum tendineum
cerebellar
cortex
198, 202
granular layer 198
middle layer 198
of Purkinje cells 198
molecular layer 198
nuclei
198
plate
198
cerebellum
195, 198
cerebral cortex
202
hemispheres
195, 199, 204
cerebrospinal fluid
195, 204
cervical sinus
63, 122
spinal nerves
195
cervix
159
213
chain of three neurons
chamber
anterior
218
fluid
218
posterior
218
chambers of eye
218
chemoattraction
12
chemotaxis
12, 16
choanae
primary
108
secondary
136
chondrocranium
77
chondrogenesis
68
chorda dorsalis
24
choriogenic side
39
chorion
37,39,45,46
frondosum
50
leave
50
chorionic cavity
224
choroid
211, 215
choroid fissures
202, 212
plexus
195, 200
238
of lateral ventricle
of third ventricle
choroidea
ciliary body
muscle
processes
circuit
foetal
placental
vitelline
claw
fold
sole
wall
cleavage
holoblastic
meroblastic
partial discoid
partial superficial
total equal
total unequal
clitoris
cloaca
cloacal membrane
club hair
cochlear duct
nerve
coelom
extraembryonic
intraembryonic
coelomic
cavities
cavity
epithelium
collecting ducts
colliculi
caudal
rostral
compaction
conducting heart system
cones of retina
conjunctiva
conjunctival sac
cono-truncus
conus medullaris
copula
cords
cellular
cortical
202
202
211
211, 216, 218
216
215
medullary
seminiferous
testicular
corium
cornea
cornua uteri
cornual processes
corona radiata
coronary cushion
coronary sinus
corpora bigemina
quadrigemina
striata
corpus
cavernosum penis
ciliare
luteum graviditatis
spongiosum urethrae
cortical area
cortical reaction
cotyledons
cranial nerves
cranium
crista terminalis
cristae ampullares
crop
crop milk
crura cerebri
cryptorchidism
crystallins
cumulus oophorus
curvature
greater
lesser
cystic duct
cytodifferentiation
cytotrophoblast
102
101
101
184
185
184
184
18
18
18
19, 34
19
18
18
164
57
60, 64, 107,
162
179
219, 220
207
36, 224
39, 224, 225
32, 224, 225
224
142
142
147
199
199
20
95
213
218
218
94
193
118
D
decidua
dental
alveoli
buds
cuticle
infundibulum
lamina
papilla
sac
spot
star
151,153
156
239
153, 156
153
153
173, 175
211, 215
159
186
7
183
90
199
199
202
163
211, 216
10
163
156
13
51
206, 207
75
90
219
135
135
199
155
215
7
125
125
130
4
51
52
114
113, 114
114
117
113
114
114
117
117
dentin
114
dentinum
113
183
dermal papillae
ridges
183, 185
dermamyotome
33, 67, 68, 82
32, 36
dermatome
dermis
173
90
descending segment
descent
of ovaries
156
of testes
153
transabdominal
153
transinguinal
153
77
desmocranium
diaphragm
84, 227
204
diaphragma sellae
73
diarthrosis
diencephalon
195, 199, 200
dioestrus
10
differentiated stage
153, 156, 159
digital cushions
183
organs
182
rays
67, 80
diphyodonts
113
directional trabecules
72
discoblastula
34
discus intervertebralis
73, 75
diverticulum Meckeli
135
diverticulum tubae auditivae 123
dorsobronchi
141
ductuli efferentes testis
151, 158
ductus allantoideus
47, 149
arteriosus Botalli
98, 102
choledochus
130
Cuvieri
225
deferens
158
epididymis
158
lactiferus
181
omphaloentericus
39
papillaris
181
reuniens
219
thyreoglossus
118, 120, 171
venosus Arantii
102
duodeno-jejunal loop
133
dura mater
203
dural venous sinuses
204
E
ear
ear bones
ear ectodermal placode
inner
middle
outer
ear ossicles
eardrum
eccrine (merocrine) glands
ectoderm
ectomeninx
ectopic pregnancy
efferent testicular tubules
egg
anisolecithal
mesolecithal
oligolecithal
polylecithal
ejaculatory duct
embryoblast
embryocystis
embryogenesis
eminentia hypobranchialis
enamel
epithelium
knot
organ
endocardial cushions
endocardial tubes
endocardium
endocrine glands
adrenal
pancreatic islets
parathyroid
external
internal
pineal
pituitary
thyroid
endoderm
endolymph
endolymphatic duct
sac
endomeninx
endomysium
endothelial layer
endothelial tube
epaxial
ependyma
epiblast
epicardium
epiceras
218
219
240
218
218, 219
218, 219, 221
218, 219
219, 222
222
180
22, 24
203
16
153, 158
18
18
18
18
158
20
22
3
118
113, 114
114
114
114
92
85
95
169
171
171
171
171
169
167
171
22, 34
219
219
219
203
82
95
86
83
191
34
95
186
epidermal appendages
epidermal layers
basal
cornified
germinative
granular
epidermal ridges
epidermal stem cells
epidermis
epidural space
epigenitale
epiglottal swellings
epimyocardial plate
epimysium
epinephrine
epiphyseal plate
epiphysis (pineal gland)
epithalamus
epithelial cords
epithelial root sheath
dermal (fibrous)
inner
outer
epithelial tubules
eponychium
epoophoron
estrogen
oestrous cycle
oestrus
ethmoidal labyrinth
Eustachian tube
eye
eyelashes
eyelids
external auditory meatus
external genitalia
F
face
Fallopian tubes
falx cerebri
fertilisation
foetal blood circuit
filum terminale
fimbriae
first polar corpuscle
fissura mediana ventralis
flexura duodenalis
flexure
cephalic
175
173
173
173
173
175
173
173
204
158
138
86, 95
82
170
70
169, 200
200
145
folding
folds
cervical
pontine (dorsal)
amniotic
cloacal
lateral
lateral anal
neural
urogenital
vestibular
vocal
folia cerebelli
follicles
follicular phase
footplates
foramen caecum
foramen ovale
forebrain
foregut
formatio reticularis
fossa ovalis
ovulationis
tonsilaris
freemartin
frog
frontal sinus
frontonasal prominence
fundus
funiculi
175
175
175
144
184
159
17
9
9
136
123, 219, 221
211
218
218
219, 222
162
195
195
57, 61
57
162
57
162
59
162
138
138
198
120
11
67, 80
118
92, 102
195, 199
57, 107, 132
199
102
156
123
17
183
186
60, 107
125
193
G
gall bladder
130
gametogenesis
4
ganglia
autonomic
205
cervico-thoracic
207
coeliac
208
cranial
205
mesenteric
208
myenteric
208
peripheral
208
pre-aortic
207
spinal
206
stellate
207
submucosal
208
sympathetic (paravertebral) 207
ganglion spirale cochleae
219
ganglion statoacusticum
219
Gartner´s duct (canal)
159
62
165
202, 204
12
102, 103
64, 193
12
8
193
133
195
241
gastrulation
gelatinous substance
genital swellings
tubercle
germinal
epithelium
disc
matrix
node
gills
glands
anal
Brunner´s
circumanal
intestinal
mammary
prostate
salivary
sebaceous
sweat
glandular proventriculus
glans penis
glioblasts
glomerular capsule
filtrate
glomeruli
external
internal
gonadal ridge
Graaphian follicle
grey matter
growth plate
guard hair
gubernaculum
gubernaculum testis
gums
guttural pouches
gyri of brain
H
haematopoietic islands
haemolymphonoduli
haemopoiesis
hair
bud
bulb
canal
cells
follicle
primary
3, 18, 22
215
162
162, 163, 164
secondary
177
growth cycle
178
papilla
175
shaft
175
handplates
67, 80
haploid cells
17
Haversian systems
73
225
head mesoderm
head plate
77, 82
heart auricles
90
bulge
90
chambers
90
plate
86
220
helicotrema
hemangioblasts
85
hemispheres
cerebellar
198
cerebral
195, 200, 201
145, 147
Henley loop
Hensen´s node
22, 34
hepatic diverticulum
cystic part
129
hepatic part
129
129
hepatic growth factor
sinusoids
129
veins
129
central
129
hepatocytes
129
hernia umbilicalis physiologica 133
hindbrain
195
hindgut
57, 107, 132
histogenesis
3
holoblastic
18
holocrine secretion
180
hoof
183
bars
183
bulbs
183
frog
183
sole
183
wall
183
stratum internum 183
externum 183
medium 183
horizontal cells
213
horn
buds
186
cavity
186
intertubular
183, 186
sheath (epiceras)
186
tubular
183
151
20, 34
175
20
120
133
133
133
133
180
158
118
177
177
135
163
192
145
146
142
142
142, 151
7
193
70
177
156
153
113
123, 222
200
129
105
86
175
175, 179
177
219
175
177
242
horns
dorsal
lateral
ventral
horny tubules
hyaloid
artery
blood vessels
canal
hyaluronidase
hymen
hyoid apparatus
hyoid arch
hyoid bone
hypaxial
hypoblast
hypodermis
hypophysis
hypothalamic nuclei
paraventricular
supraoptic
hypothalamic primordium
hippocampus
186
193
193
193
183
villi
intestine
large
small
inverted retina
iris
muscles
stroma
islets of Langerhans
isthmus
215
213
215
13
161
122
122
122
83
34
175
167
J
joints
167
167
200
202
cartilaginous
fibrous
osseous
synovial
K
keratinocyte growth factor
keratinocytes
kidney
cortex
medulla
multilobular
permanent
unilobular
I
implantation
central
48
eccentric
48
interstitial
48
incisive ducts
110, 136
foramina
110
incus
122, 219, 222
indifferent cells
153
infundibulum, neurohypophysis 167, 200
infundibulum, oviductus
159, 165
ingluvies
135
inguinal canal
153, 154
inhibitory factors
153
171
insulin
intermaxillary segment
110
interstitial lamellae
73
interthalamic adhesion
200
intertubular horn
183, 186
interventricular bundle
95
foramen
94, 200
septum
membranous
94
muscular part
94
intervertebral disc
75
intestinal glands
133
L
labia of vulva
labiogingival laminae
labioscrotal swellings
lac
lacrimal gland
sac
lactiferous ducts
lactiferous sinus
lamina
dental
labiogingival
terminalis
Langerhans cells
laryngeal cartilages
glottis
ventricles
laryngo-tracheal
groove
tube
larynx
243
133
107
107
213
211, 216
217
216
130, 171
120, 159,
165, 166
73
73
73
73
73
173
173
142, 147
147
147
147
144
147
164
113
162
180
218
110
181
181
113
113
200
174
122
138
138
137
137, 138, 141
137
lateral folds
57
layering of cerebral cortex 202
lens
capsule
215
fibers
215
lens pits
212
lens placodes
61, 212
lens vesicle
61, 212
204
leptomeninges
Lieberkühn´s crypts
133
ligamentum
arteriosum
98, 103
coronary
125, 129, 225
falciform
125, 130, 225
gastro-splenic
106
hepatoduodenale
125
hepatogastricum
125
suspensory
153
of ovary
156
teres hepatis
102
teres vesicae
102
triangular
125, 129, 225
limb buds
64
limiting membrane
external
191
internal
191
line of erosion
70
lips
113
liver
107, 129
liver capsule
129
ligaments
129
lobes
130
lobules
129
lobuli thymi
123
loop
atrial
90
bulbo-ventricular
90
duodeno-jejunal
133
midgut (intestinal) 132, 133
ascendent limb 133
descendent limb 133
of Henle
147
primitive duodenal 133
umbilical
132
lungs
138-140
avian
141
luteal phase
11
lymph centres
104
nodes
104
sacs
104
vessels
lymphatic sinuses
lingual septum
lyssa
M
macula sacculi
utriculi
magnum
major calyces
MALT
malleus
mammillary bodies
mammary bud
crest
ridge
mandible
mandibular arch
process
maturation phase
maxilla
maxillary process
meatal plug
meatus acusticus externus
Meckel´s cartilages
Meckel´s diverticulum
meconium
mediastinum
mediastinum testis
medulla oblongata
medullary area
cavity
pyramid
meiosis
Meissner´s plexus
melanin
melanoblasts
melanosomes
melatonin
membrana obturans
membrana reuniens
membrana tympani
membrane
adamantine
anal
cloacal
limiting
obturans
oropharyngeal
synovial
244
104
104
118
118
219
219
16, 165, 166
147
104
122, 219, 222
200
181
181
180
110
122
122
7
110, 122
122
222
219, 222
80, 122
40
135
225
153
195
156
72
147
4
208
173
173
173
168
222
76
123, 222
114
162
57 60
191
63, 120
57
73
tympanic
urogenital
membranous labyrinth
meninges
Merkel cells
meroblastic
mesencephalic aqueduct
mesencephalon
mesenchymal blastema
mesenchyme
mesenteries
mesentery
dorsal
ventral
mesocardium dorsale
mesoderm
mesoderm of heart plate
mesoderm somatic
mesoderm splanchnic
mesodermal plate
intermediate
lateral
paraxial
urogenital
mesoesophageum dorsale
mesogastrium
dorsal
ventral
mesogenitale
mesonephric
blastema
duct
mass
tubule
mesonephros
mesothelium
mesovarium
metamere
metamerism
metanephric blastema
metanephros
metapodium
metencephalon
metoestrus
midbrain
middle ear cavity
development
ossicles
midgut
milk
222
162
219
203
173
18
199
195
80
68
225
milk line
180
morphogenesis
3
20
morula
muscle
development
82
fibers
82
of mastication
122
smooth
82
striated
82
muscles
bisegmental
84
dorsal thoracic
83
head
84
lingual
84
papillary
95
pharyngeal
122
plurisegmental
84
of larynx
122
of limbs
84
unisegmental
83
ventral thoracic
84
muscular ventricle
135
Müller glial cells
213
158-160, 165
Müllerian ducts
inhibiting substance 158
tubercle
159
myelencephalon
195
myelinated axons
193
191
myelospongium
myenteric
ganglia
208
plexus
208
myoblasts
67
post-mitotic
82
myocardium
95
myocel
32
myofibrils
82
myofilaments
82
82
myogenesis
myogenic mesenchymal cells 82
myomere
82
myosepta
82
myotome
32, 36, 82
myotubes
82
107, 225, 227
107, 225
86
24
86
224
107, 224
32, 142
32, 36
32, 36
32, 36
124
125
125
151
144
158
144
144
142
224
156
32
32
144, 165
142, 165
67
195, 198
9
195
219
221
219
57, 107, 132
180
N
nasal
245
canals
cavity
conchae
108
136
136
passages
pits
placodes
prominences
lateral
medial
septum
Nasmyth´s membrane
nasolacrimal duct
nasolacrimal groove
nasopharynx
neocortex
nephrocoele
nephrostome
nephrotome
nerve plexuses
brachial
cervical
lumbosacral
nerve roots
dorsal
ventral
nerves
afferent
cranial
efferent
of pharyngeal arches
pelvic
sensory
somatic
spinal
splanchnic
visceral
nervous system
autonomic
enteric
parasympathetic
sympathetic
neural
canal
crest
cells
derivatives
folds
groove
plate
processes
axonal
dendritic
retina
136
108
62, 108
62, 108
62
62
110, 136
114
110
62, 110
110
202
142, 144
142
32, 36, 142
tube
neurenteric canal
neurocranium
neuroblasts
apolar
bipolar
multipolar
unipolar
neurogenesis
neurolemma
neurons
association
bipolar
commissural
post-ganglionic
pre-ganglionic
projection
pseudo-unipolar
neuropores
neuroporus
caudal
rostral
neurula
neurulation
primary
secondary
norepinephrine
notochord
notochordal
canal
plate
process
notogenesis
nuclei
basal
cuneate
gracile
olivary
ruber
somatic
visceral
nuclei of mesencephalon
myelencephalon
nucleus pulposus
206
206
26
205
205
205
205-207
205
207
208
206
205
205, 206
208
205
207
208
207, 208
207
187
30, 189
189, 205, 211
189
29, 59, 187
29
29, 187
76, 202
202
202
212
O
obturatoriae membranes
odontoblasts
oesophageal glands
246
29, 59, 187,
191
29
77, 79, 81
192, 202
192
192
192
192
191
205
202
205
202
208
207
202
205
59
29
187
187
29
29, 187
187
187
170, 207, 208
24
24, 34
24
24, 34
3, 18, 32
201
197
197
197
199
197
197
199
197
73, 75
63, 120
114
125
oesophagus
olfactory
bulbs
glands
lobe
nerve
neurons
placodes
region
tractus
oligodendrocytes
omasum
omentum
greater (majus)
lesser (minus)
omphaloenteric duct
omphaloplacenta
ontogeny
oogenesis
oogonia
operculum
ophtalmogyric muscles
optic
cup
disc
field
nerve
stalk
vesicles
organogenesis
oronasal membrane
oropharyngeal membrane
ossification
centres
centrum
primary
secondary
endochondral
intramembranous
primary
secondary
osteoblasts
osteoclasts
osteocranium
osteogenesis
osteogenic bud
osteoid
osteoprogenitor cells
ostium
107, 124
primum
secundum
osteocytes
otic capsule
pits
placodes
vesicles
ovarian cycle
oviductus
ovulation
ovulation fossa
199, 200, 202
136
200, 202
206
136
108
136
200, 202
192
127
P
palate
107, 125
107, 125
57
39
3
7
7, 156
63
218
hard
primary
secondary
soft
palatine processes
tonsil
paleocortex
paleocranium
pancreas
pancreatic body
bud
duct
head
islets
tail
papilla
papillae
filiform
foliate
fungiform
vallate
papillary body
layer of corium
muscles
parabronchi
parachordalia
paradidymis
paramesonephric duct
paranasal sinuses
paroophoron
parathormone
parathyroid gland
external
internal
pars
62, 200, 212,
213
212
211
206, 211
61, 211
61, 211
3
108, 136
57, 60, 107
67, 68
76, 77
68
70
70
68, 69, 78
68, 77
68
68, 73
68, 73
69, 73
77
68
69
68
68, 73
247
92
92
68
219
219
61, 219
219
10
159
7, 10
156
110, 136
108, 110, 136
110, 136
110
110, 136
123
202
77
107, 130
130
130
131
130
171
130
147
120
118
118
118
183, 184
175
95
141
77
158
158,159
136
159
171
123
123
123
caeca retinae
213
distalis adenohypophysis 167
foetalis placentae
50, 51
intermedia adenohypophysis 167
materna placentae
50
nervosa of pituitary 167
tuberalis adenohypophysis 167
uterina
159
218
pecten oculi
pelvis renalis
165
163
penile urethra
penis of birds
165
86, 225
pericardial cavity
pericardial-peritoneal canals 224
periderm
173
220
perilymph
219, 220
perilymphatic space
perimysium
82
162, 163
perineum
period
alveolar
140
canalicular
140
embryonic
140
hepatolienal
86
medullary
86
medulolymphatic
86
mesoblastic
86
of growth
7, 156
of maturation
7, 156
of multiplication
7, 156
pseudoglandular
140
saccular
140
periodontal ligaments
114
perioplic cushion
183
periosteum
69
peripheral nerves
afferent (sensory)
205
efferent (motor)
205
peripheral nervous system 205
peritoneal cavity
225, 227
peritubular cell aggregates 145
perivitelline space
14
permanent kidney
144
pharyngeal
arches
63, 97, 107,
120, 122
1st
63, 80, 84,
122, 218
2nd
63, 80, 84,
122, 218
3rd
63, 80, 84,
122
4th
63, 80, 84
4th and 6th 122
5th and 6th 63
complex (apparatus) 121
glands
123
grooves (clefts)
63, 107, 120,
122
1st
218, 222
membranes
63
pouches
63, 107, 120,
122
1st
122, 218, 222
2nd
123
3rd
123
4th
123
5th
123
6th
123
philtrum
110
phrenic nerve
227
phylogeny
3
pia mater
203, 204
168
pineal gland
pinealocytes
168
pituicytes
167
pituitary gland
167
placenta
37, 48, 50
apposita
51
chorioallantoic
50
choriovitelline
51, 101
cotyledonata
50, 51
deciduate
51
diffusa
50
discoidea
50
endotheliochorial
51
epitheliochorial
51
haemochorial
52
haemoendotheliochorial 52
non-deciduate
51
zonaria
50
placental barrier
50
placental circuit
101
placentom
51
placodes
lens
61
nasal
62, 108
otic
61
plate
cardiogenic
39, 86
248
plates
epiphyseal
growth
heart
intermediate
lateral
nephrogenic
notochordal
paraxial
prechordal
urogenital
70
70
86
32, 142
32, 36
142
24
32, 36
24, 34
32, 36, 142
alar
basal
floor
roof
193, 197
193, 197
193
193
140
225, 227
40
225
225, 227
225
227
225, 227
151
225
pleura
pleural cavity
pleuramnion
pleuro-pericardial fold
membrane
pleuro-peritoneal canals
folds
membranes
plica urogenitalis
plicae pleuro-peritoneales
pneumocytes
granular
membranous
polyspermy
pons Varoli
pontine nuclei
portal vein
prechordal plate
predentin
pregnancy grooves
premaxilla
preputial cavity
pre-spermatogonia
primary brain vesicles
choanae
oocyte
primary ossification
palate
urine
primitive
duodenal loop
groove
gut
nasal cavity
node
oral cavity
107
pit
22, 34
streak
22, 34
tubules
147
urogenital sinus
149
7, 156
primordial follicle
germ cells
151, 153
187
primordium of brain
of pericardial cavity 224
of spinal cord
187
processes
cornual
186
costal
77
neural
76
palatine
110
81
processus costales
neurales
76
spinosus
76
vaginalis
153
xiphoideus
77
proctodeum
60, 107
proestrus
9
progress zone
65
prominence
frontonasal
60, 107, 110
heart
59
liver
59
nasal
62
lateral
108
medial
108
mandibular 62, 80, 107, 108 110
maxillary
62, 80, 107, 108 110
pronephric duct
142
tubules
142
pronephros
1421
proper ovarian ligament
156
prosencephalon
195, 199
prostate gland
158
98
pulmonary arteries
ridge
227
pulmonary trunk
94, 98
Purkinje fibers
96
pylorus
125
140
140
16
195, 198
198
100
22
114
186
110
163
153
195
108
156
68, 72
108, 110, 136
145
R
Rathke’s pouch
Rauber´s layer
red pulp
regio
olfactoria
133
22, 34
107
108
22, 34
249
167
22
106
136
respiratoria
Reichert´s cartilages
renal corpuscle
crest
lobe
lobule
medullary pyramid
papilla
pelvis
renculus
respiratory diverticulum
primordium
rete ovarii
rete testis
reticular layer of corium
reticulum
retina
blind area
inverted
nerve fibers layer
neural
pigmented layer
rhinencephalon
rhombencephalon
rhombic lips
ribs
ridge
genital
gonadal
mesonephric
urinary
urogenital
ring of periosteal bone
rods of retina
root sheath
roots of ventral horns
rotation of midgut loop
rotation of stomach
first
second
rumen
S
saccule
satellite cells
scala
tympani
vestibuli
schizamnion
sclera
sclerotome
80, 122
144, 145
147
147
147
147
147
147
148
107, 137
137
156
153, 158
175
127
211-213
213
213
213
212, 213
213
200, 202
195
198
75, 77
scrotal pouches
scrotal raphe
scrotum
second polar corpuscle
secondary follicle
secondary ossification
sebaceous glands
segment
ascending
descending
intermaxillary
segmental arteries
semicircular ducts
anterior
lateral
posterior
seminal vesicles
seminiferous cords
seminiferous tubules
sensory nerves
organ of balance
receptors
system
septum
intermedium
primum
secundum
transversum
conotruncal
ventricular
Sertoli cells
sex determination
primary
secondary
sheath of Hertwig
of Schwann
shell gland
sino-atrial node
sinus hair
sinus horns
sinus
paranasal
urogenitalis
venosus
smooth muscle
somatic mesoderm
somatopleura
somite
144, 151
142, 151
142, 151
144
142, 144
69
213
114
193, 195
133
127
127
127
219
205
220
220
40
211, 215
250
32, 36, 68,
75, 81
163
163
163
8
7
68, 73
177, 179
90
90
110
98
219
219
219
158
153
4, 153
206
219
210
210
92
92
90, 92
225, 227
94
94
151
17
17
114
205
165, 166
95
178
90
136
149, 158
89, 90
82
224
32, 36, 224
32, 59, 68, 75
spermatids
spermatocytes
primary
secondary
spermatogenesis
spermatogonia A
spermatogonia B
spermatozoa
spermiation
spermiocytogenesis
spermiohistogenesis
spicules
spinal ganglion
spinal nerves
dorsal rami
ventral rami
spiny process
spiral ganglion of cochlea
spiral organ (of Corti)
splanchnic mesoderm
splanchnocranium
cartilaginous
membranous
splanchnopleura
spleen
spongioblasts
spongiosa
stapes
stem cells
bipotent
multipotent
sternal bars
sternebrae
sternum
stomach
rotation
ruminant
simple
stomodeum
stratum
basale
corneum
granulosum
papillare corii
reticulare corii
spinosum
striated muscle
stylopodium
subarachnoid space
subclavian artery
4, 5
subcutis
subdural space
subgerminal cavity
submucosal
ganglia
plexus
substantia nigra
sulcus
atrioventricularis
bulboventricularis
limitans
terminalis
linguae
sweat glands
swellings
genital
labioscrotal
sympathetic
ganglia
trunk
synarthrosis
synchondrosis
syncytiotrophoblast
syncytium
syndesmosis
synostosis
synovial
cavity
joints
membrane
4
4
4, 153
4
4
4, 5
4
4
4, 6
69
205, 206
206
206
206
76
219
219
224
77, 79, 81
80
80
32, 36, 224
106
192
69
122, 219, 222
45
191
191
77
77
75, 77
107, 125
125
125
125
60, 107, 113
T
tactile hair
tail bud
tarsal gland
teat
teat sinus
tectorial membrane
tectum
teeth
brachyodont
canines
deciduous
hypselodont
incisors
permanent
premolars
molars
tegmentum
tela choroidea
173
173
173
175
175
173
82
67
204
98
251
173, 175
204
34
208
208
199
89
89
193
89
118
177, 180
162, 163
162, 163
207
207
73
73
51
82
73
73
73
73
73
178
64
218
180
181
183
199
113
113
113
113
113
113
113
113
199
195
telencephalic vesicles
200
telencephalon
199, 200
179
telogen
Tenon´s space
218
tentorium cerebelli
204
7
tertiary follicle
terminal recesses
147
153
testicular lobes
151
testis determining gene
testosterone
153
200
thalamus
theca externa
7
7
theca interna
218
third eyelid
thoracic duct
104
123
thymus
118, 120,171
thyro-glossal duct
thyroid gland
171
120
thyroid hormones
thyroxine
120
tongue
118
tonsil
palatine
123
123
tonsillar crypts
sinus
123
torus linguae
118
trabeculae
69
trabeculae
cranial pair
77
directional
72
tracheal bronchus
139
rings
138
tracheo-oesophageal
grooves
137
septum
137
tractus corticoponticus
198
tractus olfactorius
200, 202
transforming growth factor α 173
trigone (trigonum vesicae) 149
triiodothyronine
120
trophoblast
20
conotruncal septa
94
tube
cardiac
86, 89
cardiogenic
86
endothelial
86
tubercula lateralia
118
tuberculum impar
118
tubotympanic recess
122, 222
tubule
distal
intermediate
proximal
tubuli recti
tubuli seminiferi contorti
tubulus
collectivus
distal
proximal
secretorius
tunica albuginea
vaginalis
tympanic cavity
tympanic membrane
external layer
U
udder
ultimobranchial body
umbilical cord
blood circuit
herniation
sac
under hairs
undifferentiated stage
urachus
ureter
ureteric bud
ureteric buds
urethra
penile
urethral groove
plate
urinary bladder
urogenital
folds
membrane
ridge
sinus
proper
urorectal septum
uterine cycle
uterovaginal canal
uterus
bicornis
bipartitus
duplex
simplex
utricle
utriculus masculinus
252
145
145
145
153
153
144
147
147
144
153, 156
154
219, 222
123, 222
219
181
123
37, 42, 57
47
133
133
177
151, 158
42, 149
165
144
165
149
163
162, 163
162, 163
149
163, 164
162
151
149, 161
149
149
10
159
159, 165
159
159
159
159
219
158
prostaticus
V
vagina
vaginal cycle
plate
valve leaflets
valves
atrioventricular
bicuspid
mitral
semilunar
tricuspid
vasculogenesis
veins
cardinal
pulmonary
umbilical
vitelline
velvet
vena cava
caudalis
cranialis
vena portae
venae omphalomesentericae
venae umbilicales
ventricle
lateral telencephalic
ventrobronchi
vermis cerebelli
vernix caseosa
vertebrae
vertebral column
vesicle
lens
optic
vesico-urethral base
vestibular glands
nerve
vestibulocochlear nerve
organ
vestibulum oris
vaginae
viscerocranium
vitelline block
blood circuit
circuit
veins
vitreous body
vomeronasal organ
158
149, 159, 165
11
161
95
95
95
95
95
95
85
W
white matter
white pulp
Wolffian duct
woven bone
193
106
144, 158, 165
68
X
xiphoid process
77
Y
Y chromosome
yolk sac
yolk sac placenta
yolk stalk
90, 101
90
89, 90, 100
89, 90, 100
186
151
37, 45, 107,
224
39
45
Z
zeugopodium
67
zona
arcuata
170
fasciculata
170
glomerulosa
170
pellucida
7
reticularis
170
zona reaction
14
zone
anal
133
cutaneous
133
ependymal
191
intermediate
133
mantle (intermediate) 191
marginal
191
of calcification
70
of hypertrophy
70
of ossification
70
zone of polarizing activity 67, 81
of proliferation
70
of resorption
70
of resting cartilage 70
osteoid
70
ventricular
191
zonular fibers
215
90, 102
90
100, 129
39, 90, 225
47
89
200
141
198
173
75
75
61
61, 195
149
164
207
207, 219
219
113
149, 161, 164
77
13
39, 45, 101
101
89, 90
215
136
253
REFERENCES AND FURTHER READING
2 Gametogenesis
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
3 Sexual maturity and sexual cycle
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
4 Fertilization
References:
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
5 Blastogenesis
References:
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
254
6 Fetal membranes and extraembryonic organs
References:
Gilbert, S.F. (2010): Developmental Biology. 9th edition, Sinauer Associates, Inc.,
Sunderland, USA.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
7 Implantation of the germ
8..Types of placenta
References:
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
9 Embryo shape development
References:
Gilbert, S.F. (2010): Developmental Biology. 9th edition, Sinauer Associates, Inc.,
Sunderland, USA.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
255
10 Skeletal system
References:
Carlson, B.M. (2004): Human Embryology and Developmental Biology. 3th edition, Mosby,
Philadelphia, USA
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
Sawad, A.A., Hana, B.A., Al-Silawi, A.N. (2009): Morphological Study of the Skeleton
Development in Chick Embryo (Gallus domesticus). Department of Biology, College of
Science, University of Basra, Basra, Iraq
11 Muscular system
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
12 Development of the blood cells , vascular system and heart
References:
Carlson, B.M. (2004): Human Embryology and Developmental Biology. 3th edition, Mosby,
Philadelphia, USA
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
256
13 Digestive system
References:
Carlson, B.M. (2004): Human Embryology and Developmental Biology. 3th edition, Mosby,
Philadelphia, USA
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are born. 8th edition,
Elsevier Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
14 Respiratory system
References:
Carlson, B.M. (2004): Human Embryology and Developmental Biology. 3th edition, Mosby,
Philadelphia, USA
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
http://people.eku.edu/ritchisong/birdrespiration.html
15 Urinary system
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
257
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
16 Genital system
References:
Gilbert, S.F. (2010): Developmental Biology. 9th edition, Sinauer Associates, Inc.,
Sunderland, USA.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
www.wisc.edu/ansci_repro/lec/lec1/female_hist.html
17 Endocrine system
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
18 Integumentary system
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
258
19 Nervous system
References:
Carlson, B.M. (2004): Human Embryology and Developmental Biology. 3th edition, Mosby,
Philadelphia, USA
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Pansky, B. (1982): Review of Medical Embryology. Macmillan, USA.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin.
Sadler, T.W. (2006): Langman´s Medical Embryology. 10th edition , Lippincott Williams
and Wilkins, Balrimore, Maryland, USA.
20 Sensory system
References:
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
Hyttel, P., Sinowatz, F., Vejlsted, M. and Betteridge, K. (2010): Essentials of domestic
animals embryology. Elsevier Saunders, UK.
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2013): Before we are bon. 8th edition, Elsevier
Saunders, UK.
Moore, K.L., Persaud, T.V.N., Torchia, M.G. (2008): The developing human. 8th edition,
Elsevier Saunders, UK.
Rüsse, I. and Sinowatz, F.(1998): Lehrbuch der Embryologie der Haustiere. 2nd edn. Parey
Buchverlag, Berlin
21 Coelom
References:
McGaedy, T..A., Quinn, P.J., FitzPatric, E.S.,Ryan, M.T. and Cahalan, S. (2006): Veterinary
embryology. Blackwell Publishing Ltd., Oxford, UK.
Horký, D., Mikyska E. (1984): Veterinární embryologie. Ediční středisko VŠV.
259
Autoři:
MVDr. Irena Kociánová, PhD.
prof. MVDr. František Tichý, CSc.
Název:
EMBRYOLOGY
Basics of embryology for veterinary medicine students
Ústav:
Ústav anatomie, histologie a embryologie
Počet stran:
Vydání:
Vydavatel:
259
1. vydání
Veterinární a farmaceutická univerzita Brno
ISBN 978-80-7305-737-4