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A TUBE ON TOP OF A TUBE

During the third and fourth weeks the top layer (ectoderm) of the trilaminar embryonic disc forms the neural plate that rolls up into a tube to form the brain and spinal cord by the process called neurulation (see Chapter 6, p. 67). Almost simultaneously, the ventral layer (endoderm) rolls down to form the gut tube, such that the embryo consists of a tube on top of a tube: the neural tube dorsally and the gut tube ventrally (Fig. 7.1). The middle layer (mesoderm) holds the two tubes

together and the lateral plate component of this mesoderm layer also splits into visceral (splanch-nic) and parietal (somatic) layers. The visceral layer rolls ventrally and is intimately connected to the gut tube; the parietal layer, together with the overlying ectoderm, forms the lateral body wall folds (one on each side of the embryo), which move ventrally and meet in the midline to close the ventral body wall (Fig. 7.1). The space between visceral and parietal layers of lateral plate mesoderm is the primitive body cavity, which at this early stage is a continuous cavity, since it

Figure 7.1 Transverse sections through embryos at various stages of closure of the gut tube and ventral body wall. A. At approximately 19 days, intercellular clefts are visible in the lateral plate mesoderm. B. At 20 days, the lateral plate is divided into somatic and visceral mesoderm layers that line the primitive body cavity (intraembryonic cavity). C. By 21 days, the primitive body cavity (intraembryonic cavity) is still in open communication with the extraembryonic cavity. D. By 24 days, the lateral body wall folds, consisting of the parietal layer of lateral plate mesoderm and overlying ectoderm are approaching each other in the midline. E. At the end of the fourth week, visceral mesoderm layers are continuous with parietal layers as a double-layered membrane, the dorsal mesentery. Dorsal mesentery extends from the caudal limit of the foregut to the end of the hindgut.

Lateral plate

Paraxial mesoderm

Intercellular clefts

Endoderm Intermediate

mesoderm

B A

Parietal mesoderm

layer

Viseral mesoderm

layer

Wall of amniotic cavity

Wall of yolk sac

Embryonic body cavity

Gut

Viseral mesoderm

C D E

Parietal mesoderm Parietal

mesoderm Connection

between gut and yolk sac Yolk sac

Amniotic cavity Surface ectoderm

Dorsal mesentery

Embryonic body cavity Viseral

mesoderm

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Chapter 7 The Gut Tube and the Body Cavities 87

has not yet been subdivided into the pericardial, pleural, and abdominopelvic regions.

FORMATION OF THE BODY CAVITY

At the end of the third week, intraembryonic mesoderm differentiates into paraxial meso-derm, which forms somitomeres and somites that play a major role in forming the skull and vertebrae; intermediate mesoderm, which contributes to the urogenital system; and lat-eral plate mesoderm, which is involved in forming the body cavity (Fig. 7.1). Soon after it forms as a solid mesodermal layer, clefts appear in the lateral plate mesoderm that coalesce to split the solid layer into two (Fig. 7.1B):

(1) the parietal (somatic) layer adjacent to the surface ectoderm and continuous with the extra-embryonic parietal mesoderm layer over the amnion. Together, the parietal (somatic) layer of lateral plate mesoderm and overlying ectoderm are called the somatopleure; (2) the visceral

(splanchnic) layer adjacent to endoderm forming the gut tube and continuous with the visceral layer of extraembryonic mesoderm covering the yolk sac (Figs. 7.1B). Together, the visceral (splanchnic) layer of lateral plate mesoderm and underlying endoderm are called the splanchnopleure. The space created between the two layers of lateral plate mesoderm constitutes the primitive body cavity. During the fourth week, the sides of the embryo begin to grow ventrally forming two lat-eral body wall folds (Fig. 7.1B and C). These folds consist of the parietal layer of lateral plate mesoderm, overlying ectoderm, and cells from adjacent somites that migrate into the mesoderm layer across the lateral somitic frontier (see Chapter 11, p. 143). As these folds progress, the endoderm layer also folds ventrally and closes to form the gut tube (Fig. 7.1D and E). By the end of the fourth week, the lateral body wall folds meet in the mid-line and fuse to close the ventral body wall (Fig.

7.1C–E). This closure is aided by growth of the head and tail regions (folds) that cause the embryo to curve into the fetal position (Fig. 7.2). Closure

Ectoderm Angiogenic cell cluster

Amniotic cavity Endoderm

Connecting stalk Cloacal membrane

Allantois

Foregut

Pericardial cavity Heart

tube

Hindgut

Remnant of the oropharyngeal

membrane Cloacal

membrane

Heart tube

Septum transversum

Septum transversum Oropharyngeal

membrane

Vitelline duct Lung bud

Liver bud

Midgut

Allantois Yolk sac A

C

B

D Oropharyngeal

membrane

Figure 7.2 Midsagittal sections of embryos at various stages of development showing cephalocaudal folding and its effects upon position of the heart, septum transversum, yolk sac, and amnion. Note that, as folding progresses, the open-ing of the gut tube into the yolk sac narrows until it forms a thin connection, the vitelline (yolk sac) duct, between the midgut and the yolk sac D. Simultaneously, the amnion is pulled ventrally until the amniotic cavity nearly surrounds the embryo. A. 17 days. B. 22 days. C. 24 days. D. 28 days. Arrows: head and tail folds.

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A B

Scrotum C

Bladder

Penis (with epispadius)

D

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Amnion Abdominal wall

Intestinal loops

Umbilical cord

B A

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Chapter 7 The Gut Tube and the Body Cavities 91

Anterior intestinal portal Primitive pericardial cavity

Lateral body wall fold Septum transversum

Hindgut

Posterior intestinal portal Intraembryonic body cavity

Closing cranial neural fold

Lung bud Pleuropericardial fold

Phrenic nerve Common cardinal vein Heart

Body wall Foregut

Sinus venosus Septum transversum Liver cords

Cloaca

Pericardio-peritoneal canals A

B C

Vitelline duct Allantois

Figure 7.5 A. Drawing showing the ventral view of an embryo at 24 days of gestation. The gut tube is closing, the anterior and posterior intestinal portals are visible, and the heart lies in the primitive pleuropericardial cavity, which is partially separated from the abdominal cavity by the septum transversum (arrow). B. Portion of an embryo at approximately 5 weeks with parts of the body wall and septum transversum removed to show the pericardioperitoneal canals. Note the size and thickness of the septum transversum and liver cords penetrating the septum. C. Growth of the lung buds into the pericar-dioperitoneal canals. Note the pleuropericardial folds.

of the body wall splits into two components (Fig. 7.6): (1) the defi nitive wall of the thorax and (2) the pleuropericardial membranes, which are extensions of the pleuropericardial folds that contain the common cardinal veins and phrenic nerves. Subsequently, descent of the heart and positional changes of the sinus

venosus shift the common cardinal veins toward the midline, and the pleuropericardial mem-branes are drawn out in mesentery-like fashion (Fig. 7.6A). Finally, they fuse with each other and with the root of the lungs, and the thoracic cavity is divided into the defi nitive pericardial cavity and two pleural cavities (Fig. 7.6B).

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92 Part 1 General Embryology

Lung Primitive pleural cavity

Parietal pleura

Visceral pleura Fibrous pericardium

Pericardial cavity

Pleuro-pericardial membrane

Parietal pleura Superior vena cava

Pleural cavity Phrenic nerve

B A

Figure 7.6 A. Transformation of the pericardioperitoneal canals into the pleural cavities and formation of the pleuropericardial membranes. Note the pleuropericardial folds containing the common cardinal vein and phrenic nerve.

Mesenchyme of the body wall splits into the pleuropericardial membranes and defi nitive body wall. B. The thorax after fusion of the pleuropericardial folds with each other and with the root of the lungs. Note the position of the phrenic nerve, now in the fi brous pericardium. The right common cardinal vein has developed into the superior vena cava.

Pleuroperitoneal fold

Septum transversum Muscular

ingrowth from body wall Inferior

vena cava

Pleuroperitoneal membrane Esophagus Aorta

Esophagus mesentery

Septum transversum Pericardioperitoneal

canal

A

B C

Figure 7.7 Development of the diaphragm. A. Pleuroperitoneal folds appear at the beginning of the fi fth week.

B. Pleuroperitoneal folds fuse with the septum transversum and mesentery of the esophagus in the seventh week, separat-ing the thoracic cavity from the abdominal cavity. C. Transverse section at the fourth month of development. An additional rim derived from the body wall forms the most peripheral part of the diaphragm.

In the adult, the pleuropericardial membranes form the fi brous pericardium.

FORMATION OF THE DIAPHRAGM

Although the pleural cavities are separate from the pericardial cavity, they remain in open communication with the abdominal (peritoneal) cavity by way of the pericardio-peritoneal canals (Fig. 7.5B). During further development, the opening between the pro-spective pleural and peritoneal cavities is closed by crescent-shaped folds, the pleu-roperitoneal folds, which project into the

caudal end of the pericardioperitoneal canals (Fig. 7.7A). Gradually, the folds extend medi-ally and ventrmedi-ally, so that by the seventh week, they fuse with the mesentery of the esophagus and with the septum transversum (Fig. 7.7B).

Hence, the connection between the pleural and peritoneal portions of the body cavity is closed by the pleuroperitoneal membranes. Further expansion of the pleural cavities relative to mes-enchyme of the body wall adds a peripheral rim to the pleuroperitoneal membranes (Fig. 7.7C).

Once this rim is established, myoblasts originat-ing from somites at cervical segments three to fi ve (C3–5) penetrate the membranes to form the muscular part of the diaphragm.

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Opening betweensternal and costal heads

Stomach Colon Left lung

Diaphragm Absence of

pleuroperitoneal membrane Aortic hiatus

Inferior vena cava

Opening for esophagus Central

tendon

A B

C

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94 Part 1 General Embryology

(vitelline) duct. The lateral body wall folds also pull the amnion with them so that the amnion surrounds the embryo and extends over the con-necting stalk, which becomes the umbilical cord (Fig. 7.1D and 7.2D). Failure of the ventral body wall to close results in ventral body wall defects, such as ectopia cordis, gastroschisis, and exstrophy of the bladder and cloaca (Fig. 7.3).

Parietal mesoderm will form the parietal layer of serous membranes lining the outside (walls) of the peritoneal, pleural, and pericardial cavities. The visceral layer will form the vis-ceral layer of the serous membranes cov-ering the lungs, heart, and abdominal organs.

These layers are continuous at the root of each organ as the organs lie in their respective cavities (This relationship is similar to the picture cre-ated when you stick a fi nger [organ] into the side of a balloon: the layer of the balloon surround-ing the fi nger [organ] besurround-ing the visceral layer;

and the rest of the balloon being the somatic or parietal layer. The space between is the “primi-tive body cavity.” The two layers of the balloon are continuous at the base [root] of the fi nger).

In the gut, the layers form the peritoneum and in places suspend the gut from the body wall as double layers of peritoneum called mesenteries (Fig. 7.1E). Mesenteries provide a pathway for vessels, nerves, and lymphatics to the organs.

Initially, the gut tube from the caudal end of the foregut to the end of the hindgut is suspended from the dorsal body wall by dorsal mesentery (Fig. 7.1E). Ventral mesentery, derived from the septum transversum, exists only in the region of the terminal part of the esophagus, the stom-ach, and the upper portion of the duodenum (see Chapter 15).

The diaphragm divides the body cavity into the thoracic and peritoneal cavities. It develops from four components: (1) septum transver-sum (central tendon), (2) pleuroperitoneal membranes, (3) dorsal mesentery of the esophagus, and (4) muscular components from somites at cervical levels three to fi ve (C3–5) of the body wall (Fig. 7.7). Since the sep-tum transversum is located initially opposite cer-vical segments three to fi ve and since muscle cells for the diaphragm originate from somites at these segments, the phrenic nerve also arises from these segments of the spinal cord (C3, 4, and 5 keep the diaphragm alive!). Congenital diaphragmatic hernias involving a defect of the pleuroperitoneal membrane on the left side occur frequently.

The thoracic cavity is divided into the peri-cardial cavity and two pleural cavities for the lungs by the pleuropericardial membranes (Fig. 7.6).

Thus, the diaphragm is derived from the fol-lowing structures:

the septum transversum, which forms the central tendon of the diaphragm;

the two pleuroperitoneal membranes;

muscular components from somites at cervical segments three to fi ve; and

the mesentery of the esophagus, in which the crura of the diaphragm develop (Fig. 7.7C).

During the fourth week, the septum transversum lies opposite cervical somites, and nerve com-ponents of the third, fourth, and fi fth cervi-cal segments of the spinal cord grow into the septum. At fi rst, the nerves, known as phrenic nerves, pass into the septum through the pleu-ropericardial folds (Fig. 7.5B). This explains why further expansion of the lungs and descent of the septum shift the phrenic nerves that innervate the diaphragm into the fi brous pericardium (Fig. 7.6).

Although the septum transversum lies oppo-site cervical segments during the fourth week, by the sixth week, the developing diaphragm is at the level of thoracic somites. The repositioning of the diaphragm is caused by rapid growth of the dorsal part of the embryo (vertebral column), compared with that of the ventral part. By the beginning of the third month, some of the dorsal bands of the diaphragm originate at the level of the fi rst lumbar vertebra.

The phrenic nerves supply the diaphragm with its motor and sensory innervation. Since the most peripheral part of the diaphragm is derived from mesenchyme of the thoracic wall, it is generally accepted that some of the lower intercostal (thoracic) nerves contribute sensory fi bers to the peripheral part of the diaphragm.

Summary

At the end of the third week, the neural tube is elevating and closing dorsally, while the gut tube is rolling and closing ventrally to create a “tube on top of a tube.” Mesoderm holds the tubes together and the lateral plate mesoderm splits to form a visceral (splanchnic) layer associ-ated with the gut and a parietal (somatic) layer that, together with overlying ectoderm, forms the lateral body wall folds. The space between the visceral and parietal layers of lateral plate meso-derm is the primitive body cavity (Fig. 7.1).

When the lateral body wall folds move ventrally and fuse in the midline, the body cavity is closed, except in the region of the connecting stalk (Figs. 7.1 and 7.2). Here the gut tube maintains an attachment to the yolk sac as the yolk sac

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Chapter 7 The Gut Tube and the Body Cavities 95

and are not covered by amnion. What is the embryological basis for this abnormality, and should you be concerned that other malfor-mations may be present?

3. Explain why the phrenic nerve, which sup-plies motor and sensory fi bers to the dia-phragm, originates from cervical segments when most of the diaphragm is in the thorax.

From which cervical segments does the nerve originate?

Problems to Solve

1. A newborn infant cannot breathe and soon dies. An autopsy reveals a large diaphragmatic defect on the left side, with the stomach and the intestines occupying the left side of the thorax. Both lungs are severely hypoplastic.

What is the embryological basis for this defect?

2. A child is born with a large defect lateral to the umbilicus. Most of the large and the small bowel protrude through the defect

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96

DEVELOPMENT OF THE FETUS The period from the beginning of the ninth week to birth is known as the fetal period.

It is characterized by maturation of tissues and organs and rapid growth of the body. The length of the fetus is usually indicated as the crown-rump length (CRL) (sitting height) or as the crown-heel length (CHL), the measurement from the vertex of the skull to the heel (standing height). These measurements, expressed in centi-meters, are correlated with the age of the fetus in weeks or months (Table 8.1). Growth in length is particularly striking during the third, fourth, and fi fth months, while an increase in weight is most striking during the last 2 months of gestation. In general, the length of pregnancy is consid-ered to be 280 days, or 40 weeks after the onset of the last normal menstrual period (LNMP) or, more accurately, 266 days or 38 weeks after fertilization. For the purposes of the following discussion, age is calculated from the time of fertilization and is expressed in weeks or calendar months.

Monthly Changes

One of the most striking changes taking place during fetal life is the relative slowdown in growth of the head compared with the rest of the body.

At the beginning of the third month, the head constitutes approximately half of the CRL (Figs.

8.1 and 8.2). By the beginning of the fi fth month, the size of the head is about one third of the CHL, and at birth, it is approximately one quarter of the CHL (Fig. 8.2). Hence, over time, growth of the body accelerates but that of the head slows down.

During the third month, the face becomes more human looking (Figs. 8.3 and 8.4). The eyes, initially directed laterally, move to the ven-tral aspect of the face, and the ears come to lie close to their defi nitive position at the side of the head (Fig. 8.3). The limbs reach their relative length in comparison with the rest of the body, although the lower limbs are still a little shorter and less well developed than the upper extremi-ties. Primary ossifi cation centers are present in the long bones and skull by the 12th week.

Also by the 12th week, external genitalia develop to such a degree that the sex of the fetus can be determined by external examination (ultrasound).

During the sixth week, intestinal loops cause a large swelling (herniation) in the umbili-cal cord, but by the 12th week, the loops have withdrawn into the abdominal cavity. At the end of the third month, refl ex activity can be evoked in aborted fetuses, indicating muscular activity.

During the fourth and fi fth months, the fetus lengthens rapidly (Fig. 8.5 and Table 8.1),

Chapter 8

Third Month to Birth: The