63
T
he embryonic period, or period of organogenesis, occurs from the third to the eighth weeks of development and is the time when each of the three germ layers, ectoderm, mesoderm, and endo-derm, gives rise to a number of specifi c tis-sues 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 develop-ment, the ectodermal germ layer has the shape of a disc that is broader in the cephalic than in the caudal region (Fig. 6.1). Appearance of the notochord and prechordal mesoderm induces the overlying ectoderm to thicken and form the neural plate (Fig. 6.2A,B). Cells of the plate make up the neuroectoderm, and their induc-tion represents the initial event in the process of neurulation.
Molecular Regulation of Neural Induction
Upregulation of fi broblast growth factor (FGF) signaling together with inhibition of the activity of bone morphogenetic protein 4 (BMP4), a transforming growth factor-b (TGF-b) family member responsible for ventral-izing ectoderm and mesoderm, causes induc-tion of the neural plate. FGF signaling probably promotes a neural pathway by an unknown mechanism while it represses BMP transcription and upregulates expression of chordin and nog-gin, which inhibit BMP activity. In the presence of BMP4, which permeates the mesoderm and ectoderm of the gastrulating embryo, ectoderm is induced to form epidermis, and mesoderm forms intermediate and lateral plate mesoderm.
If ectoderm is protected from exposure to BMPs,
its “default state” is to become neural tissue.
Secretion of three other molecules, noggin, chordin, and follistatin, inactivates BMP. These three proteins are present in the organizer (primi-tive node), notochord, and prechordal mesoderm.
They neuralize ectoderm by inhibiting BMP and cause mesoderm to become notochord and par-axial mesoderm (dorsalizes mesoderm); however, these neural inducers induce only forebrain and midbrain types of tissues. Induction of caudal neural plate structures (hindbrain and spinal cord) depends on two secreted proteins, WNT3a and FGF. In addition, retinoic acid (RA) appears to play a role in organizing the cranial-to-caudal axis because it can cause respecifi cation of cranial segments into more caudal ones by regulating expression of homeobox genes (see p. 78).
Neurulation
Neurulation is the process whereby the neu-ral plate forms the neuneu-ral tube. By the end of the third week, the lateral edges of the neural plate become elevated to form neural folds, and the depressed midregion forms the neural groove (Fig. 6.2). Gradually, the neural folds approach each other in the midline, where they fuse (Fig. 6.3A,B). Fusion begins in the cervi-cal region (fi fth somite) and proceeds cranially and caudally (Fig. 6.3C,D). As a result, the neu-ral tube is formed. Until fusion is complete, the cephalic and caudal ends of the neural tube communicate with the amniotic cavity by way of the anterior (cranial) and posterior (cau-dal) neuropores, respectively (Figs. 6.3C,D and 6.4A). Closure of the cranial neuropore occurs at approximately day 25 (18- to 20-somite stage), whereas the posterior neuropore closes at day 28 (25-somite stage) (Fig. 6.4B). Neurulation is then complete, and the central nervous system is represented by a closed tubular structure with a narrow caudal portion, the spinal cord, and a much broader cephalic portion characterized by a number of dilations, the brain vesicles (see Chapter 18).
Chapter 6
Third to Eighth Weeks: The
64 Part 1 General Embryology
Figure 6.1 A. Dorsal view of a 16-day presomite embryo. The primitive streak and primitive node are visible. B. Dorsal view of an 18-day presomite embryo. The embryo is pear-shaped, with its cephalic region somewhat broader than its caudal end.
C. Dorsal view of an 18-day human embryo. Note the primitive node and, extending forward from it, the notochord. The yolk sac has a somewhat mottled appearance. The length of the embryo is 1.25 mm, and the greatest width is 0.68 mm.
Yolk sac Cut edge
of amnion
Primitive streak
Primitive streak Primitive
node 16 days
18 days
A B
Yolk sac Amnion
Primitive node
C
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Chapter 6 Third to Eighth Weeks: The Embryonic Period 65
Cut edge of amnion
Neural plate
Neural fold
Neural groove Somite Cut edge of amnion
Primitive streak
Primitive streak
Primitive node
19 days
20 days A
C
Region of the primitive streak Neural plate (head folds) Neural groove
Primitive streak
Neural fold (head fold)
Somites 19 days
20 days B
D
Figure 6.2 A. Dorsal view of a late presomite embryo (approximately 19 days). The amnion has been removed, and the neural plate is clearly visible. B. Dorsal view of a human embryo at 19 days. C. Dorsal view of an embryo at approximately 20 days showing somites and formation of the neural groove and neural folds. D. Dorsal view of a human embryo at 20 days.
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66 Part 1 General Embryology
by active migration and displacement to enter the underlying mesoderm. (Mesoderm refers to cells derived from the epiblast and extraem-bryonic tissues. Mesenchyme refers to loosely organized embryonic connective tissue regardless of origin.) Crest cells from the trunk region leave the neuroectoderm after closure of the neural Neural Crest Cells
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 (Figs. 6.5 and 6.6), will undergo an epithelial-to-mesenchy-mal transition as it leaves the neuroectoderm
Cut edge of amnion Neural fold
Anterior neuropore Somite
Cut edge of amnion Otic placode
Posterior neuropore Pericardial bulge
Pericardial bulge 22 days
23 days A
C
Neural fold
Somites
22 days B
D
Anterior neuropore
Posterior neuropore
23 days
Figure 6.3 A. Dorsal view of an embryo at approximately day 22. Seven distinct somites are visible on each side of the neu-ral tube. B. Dorsal view of a human embryo at 21 days. C. Dorsal view of an embryo at approximately day 23. Note the peri-cardial bulge on each side of the midline in the cephalic part of the embryo. D. Dorsal view of a human embryo at 23 days.
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Chapter 6 Third to Eighth Weeks: The Embryonic Period 67
Connection with yolk sac
Connecting stalk Cut edge of amnion Pericardial
bulge
Anterior neuropore
Posterior neuropore
1st and 2nd pharyngeal
arches Pharyngeal
arches Lens
placode
Heart bulge Vitelline duct Umbilical cord
Allantois
Limb ridge Otic placode
28 days 25 days
A B
Figure 6.4 A. Lateral view of a 14-somite embryo (approximately 25 days). Note the bulging pericardial area and the fi rst and second pharyngeal arches. B. The left side of a 25-somite embryo approximately 28 days old. The fi rst three pharyngeal arches and lens and otic placodes are visible.
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 melanocytes in the skin and hair follicles, and (2) a ventral path-way through the anterior half of each somite to become sensory ganglia, sympathetic and enteric neurons, Schwann’s cells, and cells of the adrenal medulla (Fig. 6.5). Neural crest cells also form and migrate from cranial neural folds, leaving the neural tube before closure in this region (Fig. 6.6). These cells contribute to the craniofacial skeleton, as well as neurons for cranial ganglia, glial cells, melanocytes, and other cell types (Table 6.1, p. 69). Neural crest cells are so fundamentally important and con-tribute to so many organs and tissues that they are sometimes referred to as the fourth germ layer. Evolutionarily, these cells appeared at the dawn of vertebrate development and expanded this group extensively by perfecting a predatory lifestyle.
Molecular Regulation of Neural Crest Induction Induction of neural crest cells requires an inter-action at the junctional border of the neural plate and surface ectoderm (epidermis) (Fig. 6.5A).
Intermediate concentrations of BMPs are estab-lished at this boundary compared to neural plate cells that are exposed to very low levels of BMPs and surface ectoderm cells that are exposed to very high levels. The proteins nog-gin and chordin regulate these concentrations by acting as BMP inhibitors. The intermediate
concentrations of BMPs, together with FGF and WNT proteins, induce PAX3 and other tran-scription factors that “specify” the neural plate border (Fig. 6.5A). In turn, these transcription factors induce a second wave of transcription factors, including SNAIL and FOXD3, which specify cells as neural crest, and SLUG, which promotes crest cell migration from the neuroec-toderm. Thus, the fate of the entire ectodermal germ layer depends on BMP concentrations:
High levels induce epidermis formation; inter-mediate levels, at the border of the neural plate and surface ectoderm, induce the neural crest;
and very low concentrations cause formation of neural ectoderm. BMPs, other members of the TGF-b family, and FGFs regulate neural crest cell migration, proliferation, and differentiation, and abnormal concentrations of these proteins have been associated with neural crest defects in the craniofacial region of laboratory animals (see Chapter 17).
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 (Fig. 6.4B). During further development, the otic placodes invaginate and form the otic vesicles, which will develop into structures needed for hearing and maintenance of equi-librium (see Chapter 19). At approximately the same time, the lens placodes appear.
These placodes also invaginate and, during the fifth week, form the lenses of the eyes (see Chapter 20).
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68 Part 1 General Embryology
1
V VII IX
X 2
3 4-6
Figure 6.6 Drawing shows the migratory paths of neural crest cells in the head region. These cells leave the crests of the neural folds prior to neural tube closure and migrate to form structures in the face and neck (blue area). 1 to 6, pharyngeal arches; V, VII, IX, and X, epibranchial placodes.
Dorsal root ganglion Neural crest
Sympathetic ganglion
Developing suprarenal
gland
Urogenital ridge
Enteric ganglia Preaortic ganglion A
B C
Neural crest cells
D
Figure 6.5 Formation and migration of neural crest cells in the spinal cord. A,B. Crest cells form at the tips of neural folds and do not migrate away from this region until neural tube closure is complete. C. After migration, crest cells contribute to a heterogeneous array of structures, including dorsal root ganglia, sympathetic chain ganglia, adrenal medulla, and other tissues (Table 6.1, p. 69). D. In a scanning electron micrograph, crest cells at the top of the closed neural tube can be seen migrating away from this area.
In general terms, the ectodermal germ layer gives rise to organs and structures that maintain contact with the outside world:
●The central nervous system;
●The peripheral nervous system;
●The sensory epithelium of the ear, nose, and eye; and
●The epidermis, including the hair and nails.
In addition, it gives rise to:
●Subcutaneous glands,
●The mammary glands,
●The pituitary gland,
●And enamel of the teeth.
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A
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B C
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Chapter 6 Third to Eighth Weeks: The Embryonic Period 71
Somite Neural tube Intermediate mesoderm
Lateral plate mesoderm (parietal layer)
Notochord Lateral plate mesoderm (visceral layer)
Figure 6.9 Cross section through the somites and neural tube showing the organization of the paraxial mesoderm into somites and intermediate and lateral plate mesoderm.
Ectoderm Amniotic cavity Notochord
Mesoderm
Intermediate mesoderm Paraxial
mesoderm
Dorsal aorta
Neural groove
Visceral mesoderm
layer
Intermediate mesoderm
Endoderm
Somite
Intra-embryonic body cavity Parietal mesoderm
layer Amnion
Intercellular cavities in
lateral plate
A
C
B
D
Figure 6.8 Transverse sections showing development of the mesodermal germ layer. A. Day 17. B. Day 19. C. Day 20.
D. Day 21. The thin mesodermal sheet gives rise to paraxial mesoderm (future somites), intermediate mesoderm (future excretory units), and the lateral plate, which is split into parietal and visceral mesoderm layers lining the intraembryonic cavity.
in association with segmentation of the neural plate into neuromeres and contribute to mes-enchyme in the head (see Chapter 17). From the occipital region caudally, somitomeres further organize into somites. The fi rst pair of somites
arises in the occipital region of the embryo at approximately the 20th day of development (Fig. 6.2C,D). From here, new somites appear in craniocaudal sequence (Fig. 6.10) at a rate of approximately three pairs per day until, at the
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72 Part 1 General Embryology
Ectoderm
Presomites mesoderm Neural tube
Somites
Figure 6.10 Dorsal view of somites forming along the neural tube (the ectoderm has been partially removed). Somites form from unsegmented presomitic paraxial mesoderm caudally and become segmented in more cranially positioned regions.
end of the fi fth week, 42 to 44 pairs are present (Figs. 6.4B and 6.10). There are 4 occipital, 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 8 to 10 coccygeal pairs. The fi rst occipital and the last fi ve to seven coccygeal somites later dis-appear, while the remaining somites form the axial skeleton (see Chapter 10). Because somites appear with a specifi ed periodicity, the age of an embryo can be accurately determined dur-ing this early time period by countdur-ing somites (Table 6.2, p. 72).
Molecular Regulation of Somite Formation
Formation of segmented somites from unsegmen-ted presomitic (paraxial) mesoderm (Fig. 6.10) is dependent upon a segmentation clock established by cyclic expression of a number of genes. The cyclic genes include members of the Notch and WNT signaling pathways that are expressed in an oscillating pattern in presomitic mesoderm. Thus, Notch protein accumulates in presomitic mesoderm destined to form the next somite and then decreases as that somite is established. The increase in Notch protein acti-vates other segment-patterning genes that estab-lish the somite. Boundaries for each somite are regulated by retinoic acid (RA) and a combi-nation of FGF8 and WNT3a. RA is expressed
at high concentrations cranially and decreases in concentration caudally, whereas the combination of FGF8 and WNT3a proteins is expressed at higher concentrations caudally and lower ones cranially. These overlapping expression gradients control the segmentation clock and activity of the NOTCH pathway.
Somite Differentiation
When somites fi rst form from presomitic meso-derm, they exist as a ball of mesoderm (fi bro-blast-like) cells. These cells then undergo a process of epithelization and arrange them-selves in a donut shape around a small lumen (Fig. 6.11). By the beginning of the fourth week, cells in the ventral and medial walls of the somite lose their epithelial characteristics, become mes-enchymal (fi broblast-like) again, and shift their position to surround the neural tube and noto-chord. Collectively, these cells form the sclero-tome that will differentiate into the vertebrae and ribs (see Chapter 10). Cells at the dorsome-dial and ventrolateral edges of the upper region of the somite form precursors for muscle cells, while cells between these two groups form the dermatome (Fig. 6.11B). Cells from both muscle precursor groups become mesenchymal again and migrate beneath the dermatome to create
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Chapter 6 Third to Eighth Weeks: The Embryonic Period 73
TABLE 6.2 Number of Somites Correlated to Approximate Age in Days
Approximate Age (Days) Number of Somites
20 1–4
21 4–7
22 7–10
23 10–13
24 13–17
25 17–20
26 20–23
27 23–26
28 26–29
30 34–35
the dermomyotome (Fig. 6.11C,D). In addition, cells from the ventrolateral edge migrate into the parietal layer of lateral plate mesoderm to form most of the musculature for the body wall (external and internal oblique and transversus abdominis muscles) and most of the limb muscles (Fig. 6.11B; see Chapter 11). Cells in the der-momyotome ultimately form dermis for the skin of the back and muscles for the back, body wall (intercostal muscles), and some limb muscles (see Chapter 11).
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 tendon cartilage and bone component), its own myo-tome (providing the segmental muscle compo-nent), and its own dermatome, which forms the dermis of the back. Each myotome and dermatome also has its own segmental nerve component.
Molecular Regulation of Somite Differentiation Signals for somite differentiation arise from sur-rounding structures, including the notochord, neural tube, epidermis, and lateral plate meso-derm (Fig. 6.12). The secreted protein products of the noggin genes and sonic hedgehog (SHH), produced by the notochord and fl oor plate of the neural tube, induce the ventromedial por-tion of the somite to become sclerotome. Once induced, sclerotome cells express the transcrip-tion factor PAX1, which initiates the cascade of cartilage- and bone-forming genes for ver-tebral formation. Expression of PAX3, regu-lated by WNT proteins from the dorsal neural tube, marks the dermomyotome region of the somite. WNT proteins from the dorsal neural
tube also target the dorsomedial portion of the somite, causing it to initiate expression of the muscle-specifi c gene MYF5 and to form pri-maxial muscle precursors. Interplay between the inhibiting protein BMP4 (and probably FGFs) from the lateral plate mesoderm and activating WNT products from the epidermis direct the dorsolateral portion of the somite to express another muscle-specifi c gene, MYOD, and to form primaxial and abaxial muscle precursors.
The midportion of the dorsal epithelium of the somite is directed by neurotrophin 3 (NT-3), secreted by the dorsal region of the neural tube, to form dermis.
Intermediate Mesoderm
Intermediate mesoderm, which temporarily connects paraxial mesoderm with the lateral plate (Figs. 6.8D and 6.9), differentiates into uro-genital structures. In cervical and upper thoracic regions, it forms segmental cell clusters (future nephrotomes), 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 (see Chapter 16).
Lateral Plate Mesoderm
Lateral plate mesoderm splits into parietal (somatic) and visceral (splanchnic) layers, which line the intraembryonic cavity and sur-round the organs, respectively (Figs. 6.8C,D, 6.9, and 6.13A). Mesoderm from the parietal layer, together with overlying ectoderm, forms the lateral body wall folds (Fig. 6.13A). These folds, together with the head (cephalic) and tail (caudal)
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74 Part 1 General Embryology
with embryonic endoderm, forms the wall of the gut tube (Fig. 6.13B). Mesoderm cells of the parietal layer surrounding the intraembryonic cavity form thin membranes, the mesothelial membranes, or serous membranes, which will line the peritoneal, pleural, and pericardial cavities and secrete serous fl uid (Fig. 6.13B).
Mesoderm cells of the visceral layer form a thin serous membrane around each organ (see Chapter 7).
folds, close the ventral body wall. The parietal layer of lateral plate mesoderm then forms the dermis of the skin in the body wall and limbs, the bones and connective tissue of the limbs, and the sternum. In addition, sclerotome and muscle precursor cells that migrate into the parietal layer of lateral plate mesoderm form the costal cartilages, limb muscles, and most of the body wall muscles (see Chapter 11). The vis-ceral layer of lateral plate mesoderm, together
A B
C D
Neural groove
Ventral
somite wall Notochord
Intra-embryonic
cavity
Sclerotome
Sclerotome
Sclerotome
Dermatome Dermatome
Myotome
Neural tube
Dorsal aorta
Neural tube Dorsomedial muscle cells Dermatome Ventrolateral muscle cells
Figure 6.11 Stages in the development of a somite. A. Mesoderm cells that have undergone epithelization are arranged around a small cavity. B. Cells from the ventral and medial walls of the somite lose their epithelial arrangement and migrate around the neural tube and notochord. Collectively, these cells constitute the sclerotome that will form the vertebrae and ribs. Meanwhile, cells at the dorsomedial and ventrolateral regions differentiate into muscle precursor cells, while cells that remain between these locations form the dermatome. B. Both groups of muscle precursor cells become mesenchymal and migrate beneath the dermatome to form the dermomyotome B,C while some cells from the ventrolateral group also migrate into the parietal layer of lateral plate mesoderm. B. Eventually, dermatome cells also become mesenchymal and migrate beneath the ectoderm to form the dermis of the back D.
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Chapter 6 Third to Eighth Weeks: The Embryonic Period 75
Ectoderm
Wall of gut Amniotic cavity
Intraembryonic cavity
Dorsal mesentery
Visceral mesoderm
layer Parietal mesoderm
layer Serous membrane
(peritoneum) Mesonephros
Body wall
Parietal mesoderm
layer
Endoderm of yolk sac
A B
Figure 6.13 A. Cross section through a 21-day embryo in the region of the mesonephros showing parietal and visceral mesoderm layers. The intraembryonic cavities communicate with the extraembryonic cavity (chorionic cavity). B. Section at the end of the fourth week. Parietal mesoderm and overlying ectoderm form the ventral and lateral body wall. Note the peritoneal (serous) membrane.
Dermis
MYF5
MYOD
WNT
SHH NOGGIN PAX1 WNT
BMP4
Muscle PAX3
cells
Muscle cells
NT-3
BMP4
Figure 6.12 Expression patterns of genes that regulate somite differentiation. Sonic hedgehog (SHH) and noggin, secreted by the notochord and fl oor plate of the neural tube, cause the ventral part of the somite to form sclerotome and to express PAX1, which in turn controls chondrogenesis and vertebrae formation. WNT proteins from the dorsal neural tube activate PAX3, which demarcates the dermomyotome. WNT proteins also direct the dorsomedial portion of the somite to differentiate into muscle precursor cells and to express the muscle-specifi c gene MYF5. The mid-dorsal portion of the somite is directed to become dermis by NT-3 expressed by the dorsal neural tube. Additional muscle precursor cells are formed from the dorsolateral portion of the somite under the combined infl uence of activating WNT proteins and inhibitory BMP4 protein, which together activate MyoD expression.
hemangioblasts, a common precursor for vessel and blood cell formation.
Although the fi rst blood cells arise in blood islands in the wall of the yolk sac, this popula-tion is transitory. The defi nitive hematopoi-etic stem cells are derived from mesoderm surrounding the aorta in a site near the devel-oping mesonephric kidney called the aorta-gonad- mesonephros region (AGM). These cells colonize the liver, which becomes the major hematopoietic organ of the embryo and Blood and Blood Vessels
Blood cells and blood vessels also arise from mesoderm. Blood vessels form in two ways: vas-culogenesis, whereby vessels arise from blood islands (Fig. 6.14) and angiogenesis, which entails sprouting from existing vessels. The fi rst blood islands appear in mesoderm surrounding the wall of the yolk sac at 3 weeks of develop-ment and slightly later in lateral plate mesoderm and other regions (Fig. 6.15). These islands arise from mesoderm cells that are induced to form
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76 Part 1 General Embryology
Villus Amnionic cavity
Amnion
Heart Pericardial
cavity
Yolk sac Blood
island Blood vessel
Blood vessel
Chorion Connecting
stalk Allantois
Figure 6.15 Extraembryonic blood vessel formation in the villi, chorion, connecting stalk, and wall of the yolk sac in a presomite embryo of approximately 19 days.
FGF2 FGFR
VEGF VEGF-R2
(Flk1)
VEGF VEGFR1,2
(Flt1)
Artery Mesoderm
cells
Hemangioblasts Tube formation
Vein VEGF VEGF-R1
(Flt1)
Figure 6.14 Blood vessels form in two ways: vasculogenesis (top), in which vessels arise from blood islands and angiogenesis (bottom), in which new vessels sprout from existing ones. During vasculogenesis, FGF2 binds to its receptor on subpopulations of mesoderm cells and induces them to form hemangioblasts. Then, under the infl uence of VEGF acting through two different receptors, these cells become endothelial and coalesce to form vessels. Angiogenesis is also regulated by VEGF, which stimulates proliferation of endothelial cells at points where new vessels will sprout from existing ones. Final modeling and stabilization of the vasculature are accomplished by PDGF and TGF-b.
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A B
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78 Part 1 General Embryology
Ectoderm Angiogenic cell cluster
Amniotic cavity Endoderm
Connecting Cloacal
membrane stalk Allantois
Foregut
Pericardial cavity Heart
tube
Hindgut
Remnant of the oropharyngeal
membrane Cloacal
membrane
Heart tube Oropharyngeal
membrane
Vitelline duct Lung bud
Liver bud
Midgut
Allantois Yolk sac
A
C
B
D Oropharyngeal
membrane
Figure 6.17 Sagittal midline sections of embryos at various stages of development to demonstrate cephalocaudal folding and its effect on position of the endoderm-lined cavity. A. 17 days. B. 22 days. C. 24 days. D. 28 days. Arrows, head and tail folds.
DERIVATIVES OF THE
ENDODERMAL GERM LAYER The gastrointestinal tract is the main organ sys-tem derived from the endodermal germ layer.
This germ layer covers the ventral surface of the embryo and forms the roof of the yolk sac (Fig. 6.16A). With development and growth of the brain vesicles, however, the embryonic disc begins to bulge into the amniotic cavity. Lengthening of the neural tube now causes the embryo to curve into the fetal position as the head and tail regions (folds) move ventrally (Fig. 6.17). Simultaneously, two lateral body wall folds form and also move ventrally to close the ventral body wall (Fig. 6.18). As the head and tail and two lateral folds move ventrally, they pull the amnion down with them, such that the embryo lies within the amniotic cavity (Figs. 6.17 and 6.18). The ven-tral body wall closes completely except for the umbilical region where the connecting stalk and yolk sac duct remain attached (Figs. 6.17 and 6.19). Failure of the lateral body folds to close the body wall results in ventral body wall defects (see Chapter 7).
As a result of cephalocaudal growth and clo-sure of the lateral body wall folds a continuously
larger portion of the endodermal germ layer is incorporated into the body of the embryo to form the gut tube. The tube is divided into three regions: the foregut, midgut, and hindgut (Fig. 6.17C). The midgut communicates with the yolk sac by way of a broad stalk, the vitelline (yolk sac) duct (Fig. 6.17D). This duct is wide initially, but with further growth of the embryo, it becomes narrow and much longer (Figs. 6.17D and 6.18B ).
At its cephalic end, the foregut is temporarily bounded by an ectodermal–endodermal mem-brane called the oropharyngeal memmem-brane (Fig. 6.17A,C). This membrane separates the stomadeum, the primitive oral cavity derived from ectoderm, from the pharynx, a part of the foregut derived from endoderm. In the fourth week, the oropharngeal membrane ruptures, establishing an open connection between the oral cavity and the primitive gut (Fig. 6.17D).
The hindgut also terminates temporarily at an ectodermal– endodermal membrane, the cloa-cal membrane (Fig. 6.17C). This membrane separates the upper part of the anal canal, derived from endoderm, from the lower part, called the proctodeum, which is formed by an invaginat-ing pit lined by ectoderm. The membrane breaks
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Chapter 6 Third to Eighth Weeks: The Embryonic Period 79
down in the seventh week to create the opening for the anus.
Another important result of cephalocaudal growth and lateral folding is partial incorpora-tion of the allantois into the body of the embryo, where it forms the cloaca (Fig. 6.19A). The dis-tal portion of the allantois remains in the con-necting stalk. By the fi fth week, the yolk sac duct, allantois, and umbilical vessels are restricted to the umbilical region (Fig. 6.19).
The role of the yolk sac is not clear. It may func-tion as a nutritive organ during the earliest stages of development prior to the establishment of blood vessels. It also contributes some of the fi rst blood cells, although this role is very transitory. One of its main functions is to provide germ cells that reside
in its posterior wall and later migrate to the gonads to form eggs and sperm (see Chapter 16).
Hence, the endodermal germ layer initially forms the epithelial lining of the primitive gut and the intraembryonic portions of the allantois and vitelline duct (Fig. 6.19A). During further development, endoderm gives rise to:
●The epithelial lining of the respiratory tract;
●The parenchyma of the thyroid, parathyroids, liver, and pancreas (see Chapters 15 and 17);
●The reticular stroma of the tonsils and the thymus;
●The epithelial lining of the urinary bladder and the urethra (see Chapter 16); and
●The epithelial lining of the tympanic cavity and auditory tube (see Chapter 19).
Amniotic cavity Surface ectoderm
Gut
Dorsal mesente Viseral mesoderm
ry
Embryonic body cavity Connection
between gut and yolk sac Viseral
mesoderm
Parietal mesoderm
Yolk sac
A B C
Parietal mesoderm
Figure 6.18 Cross sections through embryos at various stages of development to show the effect of lateral folding on the endoderm-lined cavity. A. Folding is initiated. B. Transverse section through the midgut to show the connec-tion between the gut and yolk sac. C. Secconnec-tion just below the midgut to show the closed ventral abdominal wall and gut suspended from the dorsal abdominal wall by its mesentery. Arrows, lateral folds.
Pharyngeal pouches
Heart bulge Pharyngeal gut
Lung bud
Stomach Pancreas Primary intestinal
loop Hindgut Cloaca
Allantois Vitelline duct
Gallbladder Liver Stomodeum
B A
Urinary bladder Cloacal membrane
Figure 6.19 Sagittal sections through embryos showing derivatives of the endodermal germ layer. A. Pharyngeal pouches, epithelial lining of the lung buds and trachea, liver, gallbladder, and pancreas. B. The urinary bladder is derived from the cloaca and, at this stage of development, is in open connection with the allantois.
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