Third to Eighth Week:
The Embryonic Period
The embryonic period or period of
organogenesis,occurs from thethird to the eighth weeksof devel-opment and is
the timewhen each of the three germ layers, ectoderm, mesoderm, andendoderm, gives
rise to a number of specific tissues and organs. By the end of the embryonic
period, the main organ systems have been established, rendering the major
features of the external body form recognizable by the end of the second month.
Derivatives of the Ectodermal Germ
Layer
At the beginning of the third week of
development, the ectodermal germ layer has the shape of a disc that is broader
in the cephalic than the caudal region. Appearance of the notochord and prechordal
mesoderm induces the overlying ectoderm to thicken and form the neural plate.
Cells of the plate make up the neuroectoderm and their induction represents the
initial event in the process of neurulation.
MOLECULAR REGULATION OF NEURAL
INDUCTION
Blocking the activity of BMP-4,a TGF-βfamily
member responsible for ventralizing ectoderm and mesoderm, causes induction of
the neural plate. Thus, in the presence of BMP-4, which permeates the mesoderm and
ectoderm of the gastrulating embryo, ectoderm becomes epidermis, and mesoderm
forms intermediate and lateral plate mesoderm. If BMP-4 is absent or
inactivated, ectoderm becomes neuralized. Secretion of three other molecules,noggin,
chordin,andfollistatin, inactivates this protein. These three proteins are
present in the organizer (primitive node), notochord, and prechordal mesoderm.
They neuralize ectoderm and cause mesoderm to become notochord and paraxial mesoderm
(dorsalizesmesoderm). However, these neural inducers induce only forebrain and
midbrain types of tissues. Induction of caudal neural plate structures
(hindbrain and spinal cord) depends upon two secreted proteins,WNT-3aandFGF
(fibroblast growth factor).In addition,retinoic acid appears to play a role in
organizing the cranial-to-caudal axis be-cause it can cause respecification of
cranial segments into more caudal ones by regulating expression of homeobox
genes.
NEURULATION
Once induction has occurred, the
elongated, slipper-shaped neural plate gradually expands toward the primitive
streak. By the end of the third week, the lateral edges of the neural plate
become more elevated to form neural folds,and the depressed midregion forms the
neural groove. Gradually, the neural
folds approach each other in the midline, where they fuse. Fusion begins in the
cervical region (fifth somite) and proceeds cranially and caudally. As a
result,the neural tubeis formed. Until fusion is complete, the cephalic and
caudal ends of the neural tube communicate with the amniotic cavity by way of
the cranial and caudal neuropores,respectively. Clo-sure of the cranial
neuropore occurs at approximately day 25 (18- to 20-somite stage), whereas the
posterior neuropore closes at day 27 (25-somite stage).Neurulation is then
complete, and the central nervous system is represented by a closed tubular
structure with a narrow caudal portion, thespinal cord,and a much broader
cephalic portion characterized by a number of dilations,the brain vesicles.
As the neural folds elevate and fuse,
cells at the lateral border or crest of the neuroectoderm begin to dissociate
from their neighbors. This cell population,the neural crest, will undergo an
epithelial-to-mesenchymal transition as it leaves the neuroectoderm by active migration
and displacement to enter the underlying mesoderm. (Mesodermrefers to cells
derived from the epiblast and extraembryonic tissues.Mesenchyme refers to
loosely organized embryonic connective tissue regardless of origin.) Crest
cells from the trunk region leave the neural folds after closure of the neural
tube and migrate along one of two pathways:
1) a dorsal pathway through the
dermis, where they will enter the ectoderm through holes in the basal lamina to
form melanocytesin the skin and hair follicles and
2) a ventral pathway through the
anterior half of each somite to become sensory ganglia, sympathetic and enteric
neurons, Schwann cells and cells of the adrenal medulla. Neural crest cells also
form and migrate from cranial neural folds, leaving the neural tube before
closure in this region. These cells contribute to the craniofacial skeleton as
well as neurons for cranial ganglia, glial cells, melanocytes,and other cell
types. Induction of neural crest cells requires an interaction between adjacent
neural and overlying ectoderm.Bone morphogenetic proteins (BMPs),secreted by
non-neural ectoderm, appear to initiate the induction process. Crest cells give
rise to a heterogeneous array of tissues, as indicated in By the time the
neural tube is closed, two bilateral ectodermal thickenings,The otic placodes and
the lens placodes,become visible in the cephalic region of the embryo. During
further development, the otic placodes invaginate and form the otic
vesicles,which will develop into structures needed for hearing and maintenance
of equilibrium. At approximately the same time, the lens placo desappear. These
placodes also invaginate and, during the fifth week, form the lenses of the
eyes.
In general terms, the ectodermal germ
layer gives rise to organs and structures that maintain contact with the
outside world: (a) the central nervous system; (b) the peripheral nervous
system; (c) the sensory epithelium of the ear, nose, and eye; and (d) the
epidermis, including the hair and nails. In addi-tion, it gives rise to
subcutaneous glands, the mammary glands, the pituitary gland, and enamel of the
teeth.
Mesodermal Germ
Layer
Initially, cells of the
mesodermal germ layer form a thin sheet of loosely woven tissue on each side of
the midline. By approximately the17th day, however, cells close to the midline
proliferate and form a thickened plate of tissue known as paraxial mesoderm.
More laterally, the mesoderm layer remains thin and is known as the lateral
plate.With the appearance and coalescence of intercellular cavities in the
lateral plate, this tissue is divided into two layers :
(a)a layer continuous with mesoderm
covering the amnion, known as the somatic or parietal mesoderm layer and (b) a
layer continuous with mesoderm covering the yolk sac, known as the splanchnic
or visceral mesoderm layer. Together, these layers line a newly formed cavity,
the intraembryonic cavity, which is continuous with the extraembryonic cavity
on each side of the embryo.Intermediate mesoderm connects paraxial and lateral
plate mesoderm.
PARAXIAL MESODERM
By the beginning of the third week,
paraxial mesoderm is organized into segments. These segments, known as somitomeres,first
appear in the cephalic re-gion of the embryo, and their formation proceeds
cephalocaudally. Each somitomere consists of mesodermal cells arranged in
concentric whorls around the center of the unit. In the head region,
somitomeres form in association with segmentation of the neural plate into neuromeresand
contribute to mesenchyme in the head. From the occipital region caudally, somitomeres
further organize into somites. The first pair of somites arises in the
occipital region of the embryo at approximately the 20th day of develop-ment.
From here, new somites appear in craniocaudal sequence at a rate of approximately
three pairs per day until, at the end of the fifth week, 42 to 44 pairs are present.
There are four occipital, eight cervical, 12 thoracic, five lumbar, five
sacral, and eight to 10 coccygeal pairs. The first occipital and the last five
to seven coccygeal somites later disappear, while the remaining somites form
the axial skeleton. During this period of development, the age of the embryo is
expressed in number of somites.the approximate age of the embryo correlated to
the number of somites.By the beginning of the fourth week, cells forming the
ventral and me-dial walls of the somite lose their compact organization, become
polymor-phous, and shift their position to surround the notochord .
These cells, collectively known as
thesclerotome,form a loosely woven tissue,the mesenchyme.They will surround the
spinal cord and notochord to form the vertebral column. Cells at the
dorsolateral portion of the somite also migrate as precursors of the limb and
body wall musculature. After migration of these muscle cells and cells of the
sclerotome,cells at the dorsomedial portion of the somite proliferate and
migrate down the ventral side of the remaining dorsal epithelium of the somite
to form a new layer, the myotome. The remaining dorsal epithelium forms the
dermatome, and together these layers constitute the dermomyotome. Each
segmentally arranged myotome contributes to muscles of the back (epaxial
musculature), while dermatomes disperse to form the dermis and subcutaneous
tissue of the skin. Further more each myotome and dermatome retains its innervation
from its segment of origin, no matter where the cells migrate. Hence each
somite forms its own sclerotome(the cartilage and bone component), its
ownmyotome(providing the segmental muscle component), and its own dermatome,the
segmental skin component. Each myotome and dermatome also has its own segmental
nerve component.
INTERMEDIATE MESODERM
Intermediate mesoderm, which
temporarily connects paraxial mesoderm with the lateral plate, differentiates
into urogenital struc-tures. In cervical and upper thoracic regions, it forms
segmental cell clusters (futurenephrotomes), whereas more caudally, it forms an
unsegmented mass of tissue, the nephrogenic cord.Excretory units of the urinary
system and the gonads develop from this partly segmented, partly unsegmented
intermediate mesoderm.
LATERAL PLATE MESODERM
Lateral plate mesoderm splits into
parietal and visceral layers, which line the intraembryonic cavity and surround
the organs, respectively. Mesoderm from the parietal layer, together with
overlying ectoderm, will form the lateral and ventral body wall. The visceral
layer and embryonic endoderm will form the wall of the gut. Mesoderm cells of
the parietal layer surrounding the intraembryonic cavity will form thin membranes,
the mesothelial membranes,orserous membranes,which will line the peritoneal,
pleural, and pericardial cavities and secrete serous fluid. Mesoderm cells of
the visceral layer will form a thin serous mem-brane around each organ.
