Download The Third Week of Development The Trilaminar Germ Disc

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1. A 22-year-old woman consumes large
quantities of alcohol at a party and loses
consciousness; 3 weeks later, she misses
her second consecutive period. A
pregnancy test is positive. Should she be
concerned about the effects of her
bingedrinking episode on her baby?
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2. An ultrasound scan detects a large
mass near the sacrum of a 28-week
female fetus. What might the origin of
such a mass be, and what type of tissue
might it contain?
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3. On ultrasound examination, it was
determined that a fetus had welldeveloped facial and thoracic regions,
but caudal structures were abnormal.
Kidneys were absent, lumbar and sacral
vertebrae were missing, and the
hindlimbs were fused. What process may
have been disturbed to cause such
defects?
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4. A child has polysplenia and abnormal
positioning of the heart. How might these
two abnormalities be linked
developmentally, and when would they
have originated? Should you be
concerned that other defects might be
present? What genes might have
caused this event, and when during
embryogenesis would it have been
initiated?
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event occurring during
the third week of
gestation is gastrulation
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the process that establishes
all three germ layers
(ectoderm, mesoderm, and
endoderm) in the embryo.
Begins with the formation
of the primitive streak
on the caudal region of
the dorsal surface of
the epiblast.
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in a 15- to 16-day
embryo, it is clearly
visible as a narrow
groove with slightly
bulging regions on
either side
The cephalic end of the
streak, the primitive
node, consists of a
slightly elevated area
surrounding the small
primitive pit
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The epiblastic cells
migrate toward the
streak and on arrival
these epiblast cells
become flask
shaped and
invaginated inside
the streak. This
inward movement is
known as
invagination.
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Cell migration and specification are
controlled by (fibroblast growth factor 8)
(FGF8), which is synthesized by streak cells
themselves.
 This growth factor controls cell movement
by down regulating E-cadherin, a protein
that normally binds epiblast cells together.
 FGF8 then controls cell specification into
the mesoderm by regulating Brachyury (T)
expression
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Once the cells have invaginated, some
displace the hypoblast, creating the
embryonic Endoderm, and others come to
lie between the epiblast and newly
created endoderm to form Mesoderm.
Cells remaining in the epiblast then form
Ectoderm
 Thus, the epiblast, through the process of
gastrulation, is the source of all of the germ
layers
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As more and more cells move between
the epiblast and hypoblast layers, they
begin to spread laterally and cranially
 Gradually, they migrate beyond the
margin of the disc and establish contact
with the extraembryonic mesoderm
covering the yolk sac and amnion
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In the cephalic direction, they pass on each side of
the prechordal plate.
The prechordal plate itself forms between the tip of
the notochord and the oropharyngeal membrane
and is (derived from some of the first cells that
migrate through the node in the midline and move in
a cephalic direction).
Later, the prechordal plate will be important for
induction of the forebrain ().
The oropharyngeal membrane at the cranial end of
the disc consists of a small region of tightly adherent
ectoderm and endoderm cells that represents the
future opening of the oral cavity.
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The invaginating
mesodermal cells
spread laterally and
anteriorly to be in
contact with the
extraembryonic
mesoderm,
anteriorly these cells
surround the
prechordal plate
which is the region
lying just behind the
buccopharyngeal
membrane.
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Prenotochordal cells
invaginating in the primitive
node move forward cranially
in the midline until they reach
the prechordal plate
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These prenotochordal cells become
intercalated in the hypoblast so that for a short
time, the midline of the embryo consists of two
cell layers that form the notochordal plate ().
As the hypoblast is replaced by endoderm
cells moving in at the streak, cells of the
notochordal plate proliferate and detach from
the endoderm.
They then form a solid cord of cells, the
definitive notochord (, which underlies the
neural tube and serves as the basis for the axial
skeleton
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Because elongation of the notochord is a dynamic
process, the cranial end forms first, and caudal regions
are added as the primitive streak assumes a more
caudal position.
The notochord and prenotochordal cells extend
cranially to the prechordal plate (an area just caudal
to the oropharyngeal membrane) and caudally to the
primitive pit. At the point where the pit forms an
indentation in the epiblast, the neurenteric canal
temporarily connects the amniotic and yolk sac
cavities
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this membrane is formed of a tightly adherent
ectoderm and endoderm at the caudal end of
the germ disc with no intervening
mesoderm(ruptured at the 7th week). Its structure
is similar to that of the buccopharyngeal
membrane (ruptured at the 4th week)
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the allantois; which is
a small diverticulum
from the posterior
wall of yolk sac
extending into the
connecting stalk
during day 16.
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Although in some lower vertebrates the
allantois serves as a reservoir for
excretion products of the renal system,
 in humans, it remains rudimentary but
may be involved in abnormalities of
bladder development
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The primitive streak is organized
rostrocaudally for the formation of the
mesoderm; therefore, invaginating
epiblast cells develop into:
1.notochord at the cranial end of the
node at the primitive pit.
2.paraxial mesodermal at the lateral
margins of the node and the cranial
part of the streak.
3.the intermediate mesoderm at the
middle of the streak.
4.lateral plate of mesoderm at the
caudal part of the streak.
5.EEM extraembryonic mesoderm at
the most caudal part
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Dorsal view of the germ disc
showing the primitive streak
and a fate map for epiblast
cells.
 Specific regions of the
epiblast migrate through
different parts of the node
and streak to form
mesoderm.
 Thus, cells migrating at the
cranial most part of the node
will form the notochord (n);
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those migrating more posteriorly
through the node and cranial
most aspect of the streak will form
paraxial mesoderm (pm;
somitomeres and somites);
 those migrating through the next
portion of the streak will form
intermediate mesoderm (im;
urogenital system);
 those migrating through the more
caudal part of the streak will form
lateral plate mesoderm (lpm;
body wall); and
 those migrating through the most
caudal part will contribute to
extraembryonic mesoderm (eem;
chorion).
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The flat germ disc is initially rounded, then
after, it elongate with widening of the
cephalic part. Therefore, the shape of the
germ disc appears to be broader in the
cephalic region than the narrow caudal
region. This cephalic growth is produced by
the cephalic migration of the cells
invaginating at the primitive streak.
Therefore, cephalic germ layers start their
differentiation while the caudal germ layers
are still developing. After the forth week of
development, the invagination decrease
and the primitive streak regresses and
disappears.
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The embryonic disc, initially flat and almost round,
gradually becomes elongated, with a broad cephalic
and a narrow caudal end
Expansion of the embryonic disc occurs mainly in the
cephalic region; the region of the primitive streak
remains more or less the same size.
Growth and elongation of the cephalic part of the disc
are caused by a continuous migration of cells from the
primitive streak region in a cephalic direction.
Invagination of surface cells in the primitive streak and
their subsequent migration forward and laterally
continues until the end of the fourth week.
At that stage, the primitive streak shows regressive
changes, rapidly shrinks, and soon disappears.
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That the primitive streak at the caudal end of the
disc continues to supply new cells until the end
of the fourth week has an important bearing on
development of the embryo.
In the cephalic part, germ layers begin their
specific differentiation by the middle of the third
week, whereas in the caudal part, differentiation
begins by the end of the fourth week. Thus
gastrulation, or formation of the germ layers,
continues in caudal segments while cranial
structures are differentiating, causing the embryo
to develop cephalocaudally.
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Establishment of the Body Axes
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1.
Anteroposterior
Dorsoventral
Left-Right,
The anteroposterior axis:
is signaled by cells at the anterior (cranial) margin of the
embryonic disc.(AVE), expresses genes essential for head
formation, including the transcription factors OTX2, LIM1, and
HESX1 and the secreted factor cerberus and lefty. These
genes establish the cranial end of the embryo before
gastrulation.
The primitive streak itself is initiated and maintained by
expression of Nodal a member of the transforming growth
factor-β (TGF-β) family (TGFB) expression will induce and
maintain primitive streak. Once the streak is formed, a
number of genes regulate formation of dorsal and ventral
mesoderm and head and tail structures
Establishment of the Body Axes
2. Dorsoventral axes:
bone morphogenetic protein-4 (BMP-4) TGF-β, is secreted
throughout the embryonic disc. In the presence of this
protein and fibroblast growth factor (FGF), mesoderm will
be ventralized to contribute to
1. kidneys (intermediate mesoderm),
2. blood and body wall mesoderm(lateral plate mesoderm).
In fact, all mesoderm would be ventralized if the activity of
BMP-4 were not blocked by other genes expressed in the
node. For this reason, the node is the organizer.
Thus, chordin (activated by the transcription factor
Goosecoid ), noggin, and follistatin antagonize the
activity of BMP-4. As a result, cranial mesoderm is
dorsalized into notochord, somites, and somitomeres
Establishment of the Body Axes
Later these three genes are expressed in the
notochord and are important in neural induction in
the cranial region.
HNF-3β(hepatocyte nuclear factor) maintains the
node and later induces regional specificity in the
forebrain and midbrain areas. Without HNF-3β,
embryos fail to gastrulate properly and lack
forebrain and midbrain structures.
Goosecoid activates inhibitors of BMP-4 and
contributes to regulation of head development.
Overexpression or underexpression of this gene
results in severe malformations of the head region,
including duplications
Establishment of the Body Axes
Dorsalization in the caudal region is egulated by;
Brachyury (T) gene, this gene also block
ventralization to prduce dorsalization. Decreased
activity of this gene leads to caudal dysgenesis
(sirenomelia) of variable gedrees as dsgenesis of
the lower limbs, vertebral column, kidnies,anus, or
genitalia. This dysgenesis occur in diabetic mothers
Establishment of the Body Axes
3. Left–right sidedness:
When the primitive
streak appears,
(FGF8) is secreted by
cells in the node and
primitive streak and
induces expression of
Nodal but only on the
left side of the
embryo.
Establishment of the Body Axes
• Later, as the neural plate
is induced, FGF8
maintains Nodal
expression in the lateral
plate mesoderm, as well
as Lefty-2, and both of
these genes upregulate
PITX2 which is
responsible for
establishing left sidedness
snail
Establishment of the Body Axes
• Lefty-1 is expressed on the left side of the
floor plate of the neural tube and may act as
a barrier to prevent left-sided signals from
crossing over.
• Sonic hedgehog (SHH) may also
function in this role as well as serving as a
repressor for left-sided gene expression
on the right
Establishment of the Body Axes
• The Brachyury (T) gene, encoding a
transcription factor secreted by the
notochord, is also essential for
expression of Nodal, Lefty-1, and Lefty-2
• expression of the transcription factor Snail
is restricted to the right lateral plate
mesoderm
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By the beginning of the third week, the
trophoblast is characterized by primary
villi that consist of a cytotrophoblastic
core covered by a syncytial layer
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During further development, mesodermal
cells penetrate the core of primary villi and
grow toward the decidua. Forming the
secondary villus
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syncytiotrophoblast
cytotrophoblast
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By the end of the third week, mesodermal cells in
the core of the villus begin to differentiate into
blood cells and small blood vessels, forming the
villous capillary system .The villus is now known as a
tertiary villus or
definitive placental villus
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syncytiotrophobast
cytotrophoblast
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Capillaries in tertiary villi make contact with
capillaries developing in mesoderm of the
chorionic plate and in the connecting stalk
which in turn, establish contact with the
intraembryonic circulatory system,
connecting the placenta and the embryo
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Meanwhile, cytotrophoblastic cells in the
villi penetrate progressively into the
overlying syncytium until they reach the
maternal endometrium. Here they
establish contact with similar extensions of
neighboring villous stems, forming a thin
outer cytotrophoblast shell.
This shell gradually surrounds the trophoblast
entirely and attaches the chorionic sac
firmly to the maternal endometrial tissue
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Villi that extend from the chorionic plate to the
decidua basalis are called stem or anchoring
villi.
Those that branch from the sides of stem villi are
free (terminal) villi, through which exchange of
nutrients and other factors will occur.
The chorionic cavity, meanwhile, becomes
larger, and by the 19th or 20th day, the embryo is
attached to its trophoblastic shell by a narrow
connecting stalk which later develops into the
umbilical cord,which forms the connection
between placenta and embryo.
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Thank you 
The end 
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