Lateral Folding Of The Embryo

Embryo Liver Bud Lung

Liver bud

Midgut

Yolk sac

Liver bud

Midgut

Remnant of the buccopharyngeal membrane

Vitelline duct

Yolk sac

Figure 5.16 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. Presomite embryo. B. Embryo with 7 somites. C. Embryo with 14 somites. D. End of the first month. Note the angiogenic cell clusters in relation to the buccopharyngeal membrane.

Amnionic cavity Surface ectoderm

Amnionic cavity Surface ectoderm

Cephalocaudal Folding

Figure 5.17 Transverse 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 connection between the gut and yolk sac. C. Section just below the midgut to show the closed ventral abdominal wall and gut suspended from the dorsal abdominal wall by its mesentery.

Figure 5.17 Transverse 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 connection between the gut and yolk sac. C. Section just below the midgut to show the closed ventral abdominal wall and gut suspended from the dorsal abdominal wall by its mesentery.

(Fig. 5.16C). In the anterior part, the endoderm forms the foregut; in the tail region, it forms the hindgut. The part between foregut and hindgut is the midgut. The midgut temporarily communicates with the yolk sac by way of a broad stalk, the vitelline duct (Fig. 5.16D). This duct is wide initially, but with further growth of the embryo, it becomes narrow and much longer (Figs. 5.16D, 5.17B, and 5.20).

At its cephalic end, the foregut is temporarily bounded by an ectodermal-endodermal membrane called the buccopharyngeal membrane (Fig. 5.16, A and C). In the fourth week, the buccopharyngeal membrane ruptures, establishing an open connection between the amniotic cavity and the primitive gut (Fig. 5.16D). The hindgut also terminates temporarily at an ectodermal-endodermal membrane, the cloacal membrane (Fig. 5.16C), which breaks down in the seventh week to create the opening for the anus.

As a result of rapid growth of the somites, the initial flat embryonic disc also folds laterally, and the embryo obtains a round appearance (Fig. 5.17). Simultaneously, the ventral body wall of the embryo is established except for a small part in the ventral abdominal region where the yolk sac duct and connecting stalk are attached.

While the foregut and hindgut are established, the midgut remains in communication with the yolk sac. Initially, this connection is wide (Fig. 5.17A), but as a result of body folding, it gradually becomes long and narrow to form the vitelline duct (Figs. 5.17B and 5.18). Only much later, when the vitelline duct is obliterated, does the midgut lose its connection with the original endoderm-lined cavity and obtain its free position in the abdominal cavity (Fig. 5.17C).

Another important result of cephalocaudal and lateral folding is partial incorporation of the allantois into the body of the embryo, where it forms the

Craniocaudal Folding Images

Figure 5.18 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.

Figure 5.18 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.

cloaca (Fig. 5.18 A). The distal portion of the allantois remains in the connecting stalk. By the fifth week, the yolk sac duct, allantois, and umbilical vessels are restricted to the region of the umbilical ring (Figs. 5.18, 5.19, and 6.15).

In humans, the yolk sac is vestigial and in all probability has a nutritive role only in early stages of development (Fig. 5.20). In the second month of development, it lies in the chorionic cavity (Fig. 5.21).

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. 5.18 A). During further development, it gives rise to (a) the epithelial lining of the respiratory tract; (b) the parenchyma of the thyroid, parathyroids, liver, and pancreas (see Chapters 13 and 15); (c) the reticular stroma of the tonsils and thymus; (d) the epithelial lining of the urinary bladder and urethra (see Chapter 14); and (e) the epithelial lining of the tympanic cavity and auditory tube (see Chapter 16).

Patterning of the Anteroposterior Axis: Regulation by Homeobox Genes

Homeobox genes are known for their homeodomain, a DNA binding motif, the homeobox. They code for transcription factors that activate cascades of genes regulating phenomena such as segmentation and axis formation. Many homeobox genes are collected into homeotic clusters, although other genes also contain the homeodomain. An important cluster of genes specifying the

Figure 5.19 Human embryo (CRL 9.8 mm, fifth week) (x29.9). The forelimbs are paddle shaped.

craniocaudal axis is the homeotic gene complex Hom-C in Drosophila. These genes, which contain the Antennapedia and Bithorax classes of homeotic genes, are organized on a single chromosome as a functional unit. Thus, genes specifying more cranial structures lie at the 3' end of the DNA and are expressed first, with genes controlling posterior development expressed sequentially and lying increasingly toward the 5' end (Fig. 5.22). These genes are conserved in humans, existing as four copies, HOXA, HOXB, HOXC, and HOXD, which are arranged and expressed like those in Drosophila. Thus, each cluster lies on a separate chromosome, and the genes in each group are numbered 1 to 13 (Fig. 5.22). Genes with the same number, but belonging to different clusters form a paralogous group, such as HOXA4, HOXB4, HOXC4, and HOXD4. The pattern of expression of these genes, along with evidence from knockout

Figure 5.20 A. Lateral view of a 28-somite human embryo. The main external features are the pharyngeal arches and somites. Note the pericardial-liver bulge. B. The same embryo taken from a different angle to demonstrate the size of the yolk sac.

experiments in which mice are created that lack one or more of these genes, supports the hypothesis that they play a role in cranial-to-caudal patterning of the derivatives of all three germ layers. For example, an overlapping expression pattern of the HOX code exists in the somites and vertebrae, with genes located more 3' in each cluster being expressed in and regulating development of more cranial segments (Fig. 5.22).

External Appearance During the Second Month

At the end of the fourth week, when the embryo has approximately 28 somites, the main external features are the somites and pharyngeal arches (Fig. 5.20). The age of the embryo is therefore usually expressed in somites (Table 5.2). Because counting somites becomes difficult during the second month of development, the age of the embryo is then indicated as the crown-rump length (CRL) and expressed in millimeters (Table 5.3). CRL is the measurement from the vertex of the skull to the midpoint between the apices of the buttocks.

During the second month, the external appearance of the embryo is changed by an increase in head size and formation of the limbs, face, ears, nose, and eyes. By the beginning of the fifth week, forelimbs and hindlimbs appear as paddle-shaped buds (Fig. 5.19). The former are located dorsal to the pericardial swelling at the level of the fourth cervical to the first thoracic somites, which explains their innervation by the brachial plexus. Hindlimb buds appear slightly later just caudal to attachment of the umbilical stalk at the level of the lumbar and upper sacral somites. With further growth, the terminal portions of

Figure 5.21 Human embryo (CRL 13 mm, sixth week) showing the yolk sac in the chorionic cavity.

the buds flatten and a circular constriction separates them from the proximal, more cylindrical segment (Fig. 5.21). Soon, four radial grooves separating five slightly thicker areas appear on the distal portion of the buds, foreshadowing formation of the digits (Fig. 5.21).

These grooves, known as rays, appear in the hand region first and shortly afterward in the foot, as the upper limb is slightly more advanced in development than the lower limb. While fingers and toes are being formed (Fig. 5.23), a second constriction divides the proximal portion of the buds into two segments, and the three parts characteristic of the adult extremities can be recognized (Fig. 5.24).

Figure 5.22 Drawing showing the arrangement of homeobox genes of the Antennape-dia (ANT-C) and Bithorax(BX-C) classes of Drosophila and conserved homologous genes of the same classes in humans. During evolution, these genes have been duplicated, such that humans have four copies arranged on four different chromosomes. Homol-ogy between Drosophila genes and those in each cluster of human genes is indicated by color. Genes with the same number, but positioned on different chromosomes, form a paralogous group. Expression of the genes is in a cranial to caudal direction from the 3' (expressed early) to the 5' (expressed later) end as indicated in the fly and mouse embryo diagrams. Retinoic acid modulates expression of these genes with those at the 3' end being more responsive to the compound.

table 5.3 Crown-Rump Length Correlated to Approximate Age in Weeks

CRL (mm) Approximate Age (weeks)

10-14 6

17-22 7

28-30 8

Figure 5.23 Human embryo (CRL 21 mm, seventh week) (x4). The chorionic sac is open to show the embryo in its amniotic sac. The yolk sac, umbilical cord, and vessels in the chorionic plate of the placenta are clearly visible. Note the size of the head in comparison with the rest of the body.

Human Embryo Crl
Figure 5.24 Human embryo (CRL 25 mm, seventh to eighth week). The chorion and the amnion have been opened. Note the size of the head, the eye, the auricle of the ear, the well-formed toes, the swelling in the umbilical cord caused by intestinal loops, and the yolk sac in the chorionic cavity.

CLINICAL CORRELATES Birth Defects

Most major organs and organ systems are formed during the third to eighth week. This period, which is critical for normal development, is therefore called the period of organogenesis. Stem cell populations are establishing each of the organ primordia, and these interactions are sensitive to insult from genetic and environmental influences. Thus, this period is when most gross structural birth defects are induced. Unfortunately, the mother may not realize she is pregnant during this critical time, especially during the third and fourth weeks, which are particularly vulnerable. Consequently, she may not avoid harmful influences, such as cigarette smoking and alcohol. Understanding the main events of organogenesis is important for identifying the time that a particular defect was induced and, in turn, determining possible causes for the malformation (see Chapter 7).

Summary

The embryonic period, which extends from the third to the eighth weeks of development, is the period during which each of the three germ layers, ectoderm, mesoderm, and endoderm, gives rise to its own tissues and organ systems. As a result of organ formation, major features of body form are established (Table 5.4).

The ectodermal germ layer gives rise to the organs and structures that maintain contact with the outside world: (a) central nervous system; (b) peripheral nervous system; (c) sensory epithelium of ear, nose, and eye; (d) skin, including hair and nails; and (e) pituitary, mammary, and sweat glands and enamel of the teeth. Induction of the neural plate is regulated by inactiva-tion of the growth factor BMP-4. In the cranial region, inactivation is caused by noggin, chordin, and follistatin secreted by the node, notochord, and prechordal mesoderm. Inactivation of BMP-4 in the hindbrain and spinal cord regions is effected by WNT3a and FGF. In the absence of inactivation, BMP-4 causes ectoderm to become epidermis and mesoderm to ventralize to form intermediate and lateral plate mesoderm.

Important components of the mesodermal germ layer are paraxial, intermediate, and lateral plate mesoderm. Paraxial mesoderm forms somito-meres, which give rise to mesenchyme of the head and organize into somites in occipital and caudal segments. Somites give rise to the myotome (muscle tissue), sclerotome (cartilage and bone), and dermatome (subcutaneous tissue of the skin), which are all supporting tissues of the body. Signals for somite differentiation are derived from surrounding structures, including the notochord, neural tube, and epidermis. The notochord and floor plate of the neural tube secrete Sonic hedgehog, which induces the sclerotome. WNT proteins from the dorsal neural tube cause the dorsomedial portion of the somite to form epaxial musculature, while BMP-4, FGFs from the lateral plate mesoderm, and WNTs from the epidermis cause the dorsolateral portion to form limb and body wall musculature. The dorsal midportion of the somite becomes dermis under the influence of neurotrophin 3, secreted by the dorsal neural tube (Fig. 5.12). Mesoderm also gives rise to the vascular system, that is, the heart, arteries, veins, lymph vessels, and all blood and lymph cells. Furthermore, it gives rise to the urogenital system: kidneys, gonads, and their ducts (but not the bladder). Finally, the spleen and cortex of the suprarenal glands are mesodermal derivatives.

The endodermal germ layer provides the epithelial lining of the gastrointestinal tract, respiratory tract, and urinary bladder. It also forms the parenchyma of the thyroid, parathyroids, liver, and pancreas. Finally, the r table 5.4 Summary of Key Events During the Embryonic Period

Days

Somites

Length (mm)

Figure

Characteristic Features

Getting Back Into Shape After The Pregnancy

Getting Back Into Shape After The Pregnancy

Once your pregnancy is over and done with, your baby is happily in your arms, and youre headed back home from the hospital, youll begin to realize that things have only just begun. Over the next few days, weeks, and months, youre going to increasingly notice that your entire life has changed in more ways than you could ever imagine.

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Responses

  • Alexis
    What is lataral folding?
    2 years ago
  • hanno jalonen
    How lateral folding completed in embryo?
    10 months ago

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