Download Embryological Development of Skeletal Structures of Head and

Embryological Development of Skeletal Structures of Head and Neck
Introduction
The structural development of the head and neck occurs between the third and eighth weeks of
gestation. The 5 pairs of branchial arches, corresponding to the primitive vertebrae gill bars, that
form on either side of the pharyngeal foregut on day 22 are the embryologic basis of all the
differentiated structures of the head and neck. Each arch consists of 3 layers: an outer covering of
ectoderm, an inner covering of endoderm, and a middle core of mesenchyme. These arches are
separated further into external, ectoderm-lined pharyngeal clefts and internal, endoderm-lined
pharyngeal pouches. This article summarizes the chronologic sequence of the embryologic
development of the head and neck with respect to the branchial arches.
Periods of Prenatal Development

Proliferative period – the first 2 weeks when cell division is prevalent;

Embryonic period - from the second to the eighth weeks;

Fetal period – from the eighth week to birth.
Week 1
After the sperm enters the oval cytoplasm in the uterine tube, the maternal and paternal
chromosomes combine to form a zygote, completing fertilization. The ciliary action of the uterine
tube transports the zygote to the uterus, during which it undergoes a series of mitotic divisions and
transforms into the ball of small cells termed blastomeres. By the time they reach the uterus in
approximately 3 days, the blastomeres become morula, a ball of 16 cells (after 4 mitotic divisions),
and begin to form an internal cavity.[1]
Thus formed, the blastocyst consists of two layers of cells, an inner layer termed the embryoblast
that becomes the embryo and an outer layer termed the trophoblasts that forms the embryonic part
of the placenta. At approximately day 5, the blastocyst attaches to the endometrium in the posterior
wall of the uterus, and at approximately day 6, the trophoblasts differentiate into
syncytiotrophoblasts and cytotrophoblasts. The syncytiotrophoblasts then penetrate the endometrial
epithelium and invade the underlying endometrial stroma; by the end of the first week, the
superficial implantation of the blastocyst is complete.
Week 2
During the second week, a rapid proliferation and differentiation of the trophoblasts occurs. The
decidual reaction of the endometrial tissues to accommodate the blastocyst implantation becomes
accelerated during this week. At approximately day 9, the blastocyst is embedded completely
beneath the endometrial epithelium, and spaces appear in the syncytiotrophoblasts that in 2 days
form the lacunae network by fusion. The syncytiotrophoblast erosion into the endometrial blood
vessels marks days 11 and 12.
Thus formed, uteroplacental circulation allows the maternal blood into the syncytiotrophoblast
lacunae networks. Also in days 11 and 12, the primary yolk sac forms and part of the cytotrophoblast
differentiates into extraembryonic mesoderm. The extraembryonic coelom derived from the
extraembryonic mesodermal space eventually grows into the chorionic cavity.
By the end of week 2, the development of primary chorionic villi is observed, the primary yolk sac
is replaced by the secondary yolk sac, and the amniotic cavity appears as a space between the
cytotrophoblasts and the inner cell mass. The inner cell mass further differentiates into a bilaminar
embryonic disc. The outer layer, the epiblast, is related to the amniotic cavity. The inner layer, the
hypoblast, lies adjacent to the blastocyst cavity, and its localized thickening, the prochordal plate,
becomes the future embryonic cranial region.
Week 3
The third week is marked by the formation of the trilaminar embryonic disc by the process of
gastrulation; the inner layer is termed endoderm, the middle layer, mesoderm, and the outer layer,
ectoderm. The embryo begins as a two-dimensional planar structure, and just prior to the third
week, the stage is set for the development of the central nervous system in the area of ectoderm
thickening known as the neural plate.
Gastrulation
1. Towards 14 days the primitive ectoderm thickens - formed "primitive plaque";
2. There formed "primitive groove”;
3. In the cranial edge is formed "primitive node";
4. The cells of the primitive groove and node acquire mitotic activity;
5. They divide and penetrate between the ectoderm and endoderm.
A midsagittal groove appears as a result of invagination of the ectoderm centrally and
simultaneous elevation of ectodermal tissue alongside the groove to form the neural folds. These
folds then fuse with each other in the mid line beginning at the junction of the future brain and spinal
cord to form the neural tube. As the folds fuse, the neural tube separates from the overlying
ectoderm from which it is derived.
A population of ectodermal cells adjacent to the neural fold and not included in the overlying
surface (somatic) ectoderm gives rise to the formation of the neural crest. These neuroectodermal
crest cells are believed to migrate widely throughout the developing embryo in a relatively cell-free
enriched extracellular matrix and differentiate into a wide array of cell and tissue types, influenced
by the local environment. Most connective and skeletal tissues of the cranium and face ultimately
come from the derivatives of neural crest cells.
The first morphologic evidence of the optic primordia is seen as a thickened area with a shallow
sulcus on the lateral forebrain of the neural tube in the region of the future diencephalon. During this
week, the optic sulcus deepens and the surrounding walls form an invagination, which at first is in
contact with the overlying ectoderm. Neural crest cells intervene between the optic vesicle and the
overlying ectoderm and give rise to specialized neuroectodermal elements of the eye and
adnexum.[2]
As the neural tube fuses cranially, closing off the anterior neuropore, a mesencephalic flexure
occurs and the major divisions of the brain—prosencephalon (forebrain), mesencephalon (midbrain),
and rhombencephalon (hindbrain)—can begin to be distinguished. By the end of the third week,
further growth of the cephalic portion of the neural tube gives rise to the frontal nasal process and
the branchial arches, the first stages of a recognizable face.
Week 4
By the end of the third week-trilaminar embryonic disc has a definite orientation;
- During the fourth week - embryo begins to form a tubular structure;
-In front of the primitive streak is the primitive node – mesodermal cells that will form the
Notochord;
-Also have differentiation of cells from the ectoderm forms the neuroectoderm:
-a neural plate forms ;
-this plate thickens with proliferation ;– Invaginates centrally and forms the neural groove:
-this groove deepens and is surrounded by the two neural folds;
-development of the neural crest cells from these neural folds.
The neural crest

As the neural tube forms, a group of cells separate from the neuroectoderm;

These cells have the capacity to migrate and differentiate extensively within the developing
embryo;

They are the basis for nerves structures;

Neural crest cells in the head region have an important role:

They also differentiate to form most of the connective tissue of the head;

Embryonic connective tissue elsewhere is derived from mesoderm and is
known as mesenchyme;

Whereas in the head it is known as ectomesenchyme, reflecting its origin
from neuroectoderm.

Neural crests cells divide rapidly;

They are formed three cell flow with different biological function :

First group - develops at the site of its formation;

Second group – formes a migratory flows;

Third group - intended to be absorbed and stimulates differentiation of the
surrounding tissue.
Brachial arches
1.
2.
3.
4.
5.
6.
7.
8.
Separated laterally by branchial grooves/clefts;
Medially they are separated by pharyngeal pouches;
First arch (mandibular arch) – maxillary and mandibular processes;
Second arch (hyoid arch) - hyoid bone, part of the temporal bone (VII nerve)
a. cartilage = Reichert’s cartilage;
b. the mesoderm of this arch will form the muscles of facial expression, the middle ear
muscles;
Third arch –tongue (IX nerve);
Fourth arch –tongue, most of the laryngeal cartilages (IX and X nerves);
Fifth arch – becomes incorporated into the fourth;
Sixth arch – most of the laryngeal cartilages (IX and X nerves).
The recognizable face begins its development from 5 primordia that surround a central area of
depression, the oral pit or the stomadeum. These primordia are the single cranially located frontal
nasal process and two bilaterally located maxillary processes and mandibular processes. The
maxillary and mandibular processes are derived from the first branchial arch. The first branchial arch,
also termed the mandibular arch, forms the lateral wall and base of the stomadeum, the primitive
mouth that appears as a slight depression of the ectoderm surface.[4]
The remaining branchial arches constitute the lateral and anterior walls of the primitive
oropharynx, with the corresponding pharyngeal pouches between them. These processes or masses
grow differentially, and by obliterating the ectodermal plates or grooves between them eventually
give rise to the features of the face.[4]
The mandibular processes are the first to merge with each other at the mid line and eventually
give rise to the mandible and the lower part of the face and tongue. The dorsal end of the first arch
cartilage, also termed Meckel cartilage, ossifies to form the malleus and incus of the middle ear. The
dorsal end of the second arch cartilage, also termed Reichert cartilage, ossifies to form the stapes of
the middle ear and the styloid process of the temporal bone. Small elevations at the dorsal ends of
the first and second arches surrounding the first branchial groove fuse together to form the auricle of
the external ear. The third branchial arch is not involved with the development of the ear.
The most common congenital anomaly of the branchial clefts is remnants of the second branchial
cleft. The external component is found at the anterior junction of the middle and lower thirds of the
sternocleidomastoid muscle and its track usually passes over the glossopharyngeal nerve and
between the internal and external carotid arteries to the tonsillar fossa. The entire track and fossa
must be excised. Cysts of the first branchial cleft are much less common but should be considered
when excising a mass above the hyoid bone. Its course may involve the branches of the facial nerve.
The third branchial cleft is rare but externally it may present at the same region as the second. It
courses under the internal carotid artery.
During the fourth week, the primitive trisegmented brain further subdivides. The prosencephalon
(forebrain) divides into the telencephalon (endbrain) with prominent lateral domes (cerebral
hemispheres) and the diencephalon, which gives rise to the optic vesicles. The mesencephalon
remains undivided and in the flexed cephalic flexure. The rhombencephalon divides into the
mesencephalon (cerebellum, pons) and the myelencephalon (medulla). By the end of the fourth
week, the fundamental organization of the future brain is clearly identifiable.
The ectoderm overlying the optic vesicle of the developing eye thickens to form the lens placode.
During this week, the optic vesicle deepens to form a goblet-shaped double-layered optic cup, as its
stem narrows to form the optic stalk in continuity with the diencephalon. The frontal nasal process
intervenes between the two lateral optic cups and at this stage the developing eyes are nearly 180°
apart.
Week 5
Toward the end of the fourth week, nasal placodes develop bilaterally at the inferolateral corners
of the frontonasal process. As the region surrounding the nasal placodes develops into medial and
lateral nasal processes, the deepening nasal placodes are transformed into nasal pits, in time forming
the anterior nares. With continued ectodermal development, the nasal placodes become olfactory
grooves that at this stage are in continuity with the developing oral cavity. The maxillary processes
continue to enlarge, encroaching on the stomadeum, to form a primitive oral cavity
The first branchial arch gives rise to muscles of mastication (temporalis, masseter, lateral
pterygoid, medial pterygoid). The mylohyoid, anterior belly of digastric, tensor tympani, and tensor
veli palatini muscles also are derived from the first branchial arch. The second branchial arch
develops into the muscles of facial expression.
The tongue is derived from the first through the fourth branchial arches. At the end of the fourth
week, a median swelling, also termed median tongue bud, appears in the floor of the primitive
pharynx just rostral to the foramen cecum. This is followed by a pair of lateral lingual swellings, also
termed distal tongue buds, that arise from the proliferation of the ventromedial first branchial arches
on each side of the median swelling. The distal tongue buds rapidly grow and fuse to form the
anterior two thirds of the tongue, while the median tongue bud atrophies and forms no recognizable
part of the adult tongue.
The posterior one third develops from the copula formed by the ventromedial part of the second
branchial arches caudal to the foramen cecum and the hypopharyngeal eminence formed caudal to
the copula from the ventromedial part of the third and fourth branchial arches. As the embryonic
tongue further develops, the copula atrophies and disappears.
The general mucosal sensory innervation of the anterior two thirds of the tongue, derived from
the first arch, is from the lingual branch of the trigeminal nerve, the nerve of the first branchial arch.
The chorda tympani branch of the facial nerve, the nerve of the second branchial arch, supplies the
taste buds of the anterior two thirds of the tongue, except the vallate papillae.
The glossopharyngeal nerve, the nerve of the third branchial arch, supplies the taste buds in the
vallate papillae and most of the posterior one third of the tongue mucosal surface. The superior
laryngeal branch of the vagus nerve, the nerve of the fourth branchial arch, innervates a small patch
of the tongue mucosal surface anterior to the epiglottis. All intrinsic and extrinsic tongue muscles,
with the exception of the palatoglossus muscle, are supplied by the hypoglossal nerve. The
palatoglossus muscle is supplied by the pharyngeal plexus fibers from the vagus nerve.
As the optic stalk narrows further to define the primitive optic nerve, retinal pigment appears in
the external layer of the optic cup and the inner layer begins to differentiate into the neural
elements of the retina. The primitive vitreous body develops in the intervening space as the lens
placode invaginates toward the optic cup to form a lens vesicle, detaching itself from the overlying
ectoderm.
As the features of the face form, the development of the embryonic skull begins. The
mesenchyme surrounding the developing primitive brain condenses to form a mesenchymal capsule,
the desmocranium. At approximately the fifth week, the base thickens, forming the cartilaginous
cranial base through neuroectodermal condensation of the mesenchyme. In contrast, the calvaria
develops by direct membranous ossification without a cartilaginous precursor later in the embryonic
period. See the images below.
Week 6
The medial nasal processes approach each other to form a single globular process that in time
gives rise to the nasal tip, columella, prolabium, frenulum, and the primary palate. As this occurs, the
frontonasal process collapses inward to form the nasal septum. Continued growth of the maxillary
mass below the optic vesicles allows fusion with the lateral nasal process. As fusion occurs, a sinking
troughlike epithelial groove demarcates the naso-optic furrow connecting the conjunctival lacrimal
sac with the lateral nasal wall. The epithelial groove fuses as a solid epithelial cord and eventually
canalizes later in fetal development to become the nasolacrimal duct.
Toward the end of the sixth week, the maxillary process fuses with the medial nasal fold of the
globular process, forming a true nostril as it gives rise to the lateral lip element. However, posterior
to this anterior fusion of the maxillary process to the nasal processes, the developing nasal floor is
open to the oral cavity. Within the primitive stomadeum, lateral palatine processes develop from the
medial edges of the maxillary process to give rise to the secondary palate. At this stage, the
developing tongue nearly fills the oronasal cavity completely and reaches the nasal septum.
Simultaneously, the eye continues its development as neural crest mesoectodermal cells at the
lateral aspect of the lens differentiate into the early cornea and sclera. The cavity of the optic stalk is
obliterated as nerve fibers from the retina grow back to reach the brain to form the optic nerve. The
overlying surface ectoderm develops subtle horizontal folds, with mesenchymal core above and
below the developing cornea representing the beginning of the upper and lower eyelids.
During this sixth week, the external ear develops from 6 mesenchymal swellings (hillocks) that
surround the first branchial cleft. The first 3 hillocks arise from the mandibular arch (first branchial
arch); the second 3, from the hyoid arch (second branchial arch). From ventral to dorsum, the hillocks
of the first arch become the tragus, helix, and the cymba concha; the hillocks on the second arch
become the antitragus, antihelix, and concha. The branchial cleft lengthens to form the primordium
of the external auditory canal. As the face develops, the auricle gradually is repositioned to a more
lateral cephalic position from the original location low on the side of the neck.
Week 8
By the eighth week, the face has acquired a more human appearance, with complete closure of
the lower facial fissures or grooves. The primitive upper and lower jaws are formed with the
complete fusion of the maxillary and mandibular processes. The upper lip and lower nasal regions are
better defined. As it lengthens vertically, the frontonasal process continues to collapse horizontally,
forming a transverse furrow at the nasal bridge. As the frontocranial region loses its overhang, the
eyes begin to take a more medial position. The anterior rotation of the eyes continues throughout
the remainder of the gestational period and well into childhood.
The upper and lower lids continue to develop and assume a more almond shape as they begin to
fuse with each other (separation of the lids not occurring until weeks 25-26). The lined ectodermalderived epithelium between the fused eyelids and the cornea develops into the conjunctival sac, and
from the superior-lateral angles, the lacrimal glands develop.
The development of the skull continues, with ossification centers arising within the mesenchyme
(membranous ossification) adjacent to the developing brain to form the flat bones of the calvarial
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
fetal life.
In the face, small nasal bones appear above the nasal capsule, the cartilaginous model. On the
lateral surface of the nasal capsule, premaxillary and maxillary ossification centers appear.
Posterior-lateral to the developing maxillary bone, ossification centers arise within the zygomatic
and squamoid portion of the temporal region. The mesenchyme encompassing Meckel cartilage
undergoes membranous ossification to form the body of the mandible. In time, the Meckel cartilage
disappears and persists as the incus and malleus of the middle ear. The onset of bone formation
marks the end of the embryonic period and the developing fetus generally is much more resistant to
teratogenic insults.
Within this short period of 5 weeks, when the mother may be unaware of her own pregnancy,
the face of her child has emerged. Any error that occurs in these tightly sequenced events of early
facial embryogenesis can have significant consequences.
By whatever causative factor, failure of the lateral maxillary process to fuse with the central
globular process is expected to result in a unilateral cleft of the upper lip. Similarly, the median cleft
can be explained by incomplete merging of the median nasal processes, and an oblique facial cleft
can be explained by persistence of the groove between the maxillary process and the lateral nasal
process (medial canthal region to the ala of the nose).
While the occurrence of some facial clefts[7] can be understandable in terms of failure of fusion
of the various primordial facial processes, others are not readily explainable in such terms. A cleft
that begins lateral to the philtrum and extends to the mid portion of the lower eyelid is difficult to
explain. Events prior to the normal process of fusion may lead to localized areas of tissue deficiency,
possibly resulting in these atypical clefts.
Differences of opinion exist in the literature as to what fusion means in embryogenesis and how
cell proliferation, cell differentiation, cell degeneration, and the extracellular matrix are involved in
morphogenesis.