Development of 11 Gastrointestinal Tract Learning Objectives At the end of this chapter, students would be able to define and understand the following: • Development of the esophagus and stomach • Rotation of the midgut loop • Development of the pancreas • Formation and fate of the cloaca • Anorectal anomalies Keywords: Tracheoesophageal fistula, annular pancreas, imperforate anus, pectinate line. part of the yolk sac is incorporated into the Introduction embryo to form the primitive gut. Primitive gut is divisible into foregut, Gastrointestinal tract (GIT) extends from midgut, and hindgut (Fig. 11.1). We will now the stomodeum (an ectodermal depression discuss the parts of GIT under each one of at cranial end) to the proctodeum (an ecto­ them. dermal depression at caudal end) of the embryo. Thus, lining of terminal parts is ecto­ dermal in origin, while rest of it is formed by Foregut the endoderm of the yolk sac. The surrounding splanchnic mesenchyme forms the connec­ The derivatives of foregut are pharynx, tive tissue and muscular elements of the wall esophagus, stomach, duodenum (proximal to of the gut. The development of tongue, tooth, the opening of bile duct), liver, biliary appa­ and palate is dealt in Chapter 10. ratus, and pancreas. These derivatives of the foregut except the pharynx, lower respira­ tory tract, and most of the esophagus are supplied by celiac artery, which is the artery Formation of the of the foregut. Primitive Gut Midgut During the fourth week, the embryo under­ goes folding both cephalocaudally as well as The derivatives of the midgut are duodenum laterally. Because of this folding, the dorsal distal to the opening of the bile duct, jejunum, 106 Chapter 11 Pharynx Stomodeum Gastric and duodenal region Septum transversum Heart Yolk stalk Coeliac trunk (foregut A.) Allantois Superior mesenteric artery (midgut A.) Cloacal membrane Cloaca Inferior mesenteric artery (hindgut A.) Fig. 11.1 Section of the early embryo after folding showing the three parts of GIT: foregut, midgut, and hindgut along with their blood supply. ileum, cecum and appendix, ascending colon, Table 11.1 lists the parts of the GIT and and right two­thirds of the transverse colon. the associated transcription factors. These derivatives are supplied by the supe­ There seems to be reciprocal interac­ rior mesenteric artery, which is the artery of tion between the endoderm and splanchnic the midgut. mesoderm. This is initiated by sonic hedgehog (SHH) expression. This then causes Hindgut Table 11.1 Transcription factors associated The derivatives of the hindgut are left one­ with the development of various parts of the third of transverse colon, descending colon, GIT sigmoid colon, rectum, and upper two­thirds Transcription of the anal canal above the pectinate line. Part of the gut tube factor These derivatives of the hindgut are supplied by the inferior mesenteric artery, which is Esophagus and stomach SOX2 the artery of the hindgut. Duodenum PDX1 The development of different parts of Small intestine CDXC the gut is governed by various transcription factors. Large intestine and rectum CDXA Development of Gastrointestinal Tract 107 expression of Hox genes in the mesoderm septum and communication of lumens which brings in the differentiation of the of the two tubes: the trachea and endoderm in different regions such as small esophagus (Fig. 11.3). intestine, colon, cecum, etc. 2. Short esophagus: It results from the We will now consider the fate of each failure of the esophagus to elongate. part of the primitive gut sequentially starting This draws a part of the stomach into from the foregut. the thorax through esophageal hiatus The foregut starts with the pharynx, in the diaphragm causing congenital which has been dealt with pharyngeal appa­ hiatal hernia. ratus in Chapter 10. The subsequent parts, that is, esophagus, stomach, and duodenum shall now be considered. Development of the Stomach Development of the It appears as a fusiform dilatation along the Esophagus caudal part of the foregut around the fourth week. It is initially oriented in the median The primitive pharynx shows appearance of plane. It presents two ends: the proximal and folds called tracheoesophageal folds from the distal; two borders: the ventral and the its lateral walls. They fuse to form tracheo­ dorsal; two folds: the ventral mesogastrium esophageal septum which divides pharyn­ and the dorsal mesogastrium, anchoring the geal gut into ventrally placed trachea and borders of the stomach to the respective dorsally placed esophagus. In the beginning, abdominal walls; and two surfaces: right and the esophagus is short. It elongates due to left (Fig. 11.4). growth of the body, development and descent of heart and lungs, and reaches its definitive Rotation of the Stomach relative length by about the seventh week. Its epithelium and the glands are derived The stomach undergoes 90­degree rotation from the endoderm while connective tissue around its own longitudinal axis, and with and the muscular elements of its wall are this the following occurs: derived from the surrounding splanchnic 1. Its ventral border goes to the right mesenchyme. However, the striated muscle side, grows less, and forms the lesser in the wall of the upper third of the esoph­ curvature. agus is contributed by the branchial meso­ 2. Its dorsal border goes to the left side, derm. During the course of development, grows more, and forms the greater the epithelium proliferates to obliterate the curvature. lumen. This is then followed by vacuolization 3. Its right surface becomes posterior and recanalization (Fig. 11.2). Its failure can surface and is innervated predomi­ cause esophageal stenosis or atresia. nantly by the right vagus nerve. 4. Its left surface becomes anterior Anomalies surface and is innervated mainly by the left vagus nerve. 1. Esophageal atresia: It occurs due After the rotation, the stomach assumes to the failure of recanalization. It is its final position. Its proximal end sinks usually associated with tracheoesoph­ downward and to the left and forms the ageal fistula. The malformation results cardiac end, while the distal end goes toward from deviation of tracheoesophageal right and forms the pyloric end. 108 Chapter 11 Level of section b Primitive pharynx Laryngotracheal diverticulum Tracheo-oesophageal fold Pharynx Primordium of laryngo-tracheal tube a b Level of section d Lung bud Tracheo-oesophageal Folds fused fold Oesophagus d c Level of section f Oesophagus Laryngotracheal tube Laryngotracheal tube f e Fig. 11.2 (a–f) Illustrations showing development of oesophagus.Note how tracheo- esophageal septum develops at 4 to 5-weeks separating esophagus and the laryngotracheal tube. Development of Gastrointestinal Tract 109 Esophageal Trachea atresia Fistula Esophagus abcd Fig. 11.3 (a–d) Illustrations showing schematic representation of various types of tracheoesophageal fistula. Longitudinal axis Lesser curvature Stomach Greater curvature Duodenum abc Fundus Anteroposterior axis Duodenum Body Pylorus d e Fig. 11.4 (a–e) Illustrations showing the development and rotation of the stomach. 110 Chapter 11 Fate of the Mesogastrium 2. The part between the liver and the stomach forms lesser omentum. In the ventral mesogastrium, liver develops. Likewise, the spleen develops in the With this, the following changes occur: dorsal mesogastrium. This splits the dorsal 1. The part of the ventral mesogas­ mesogastrium into (1) gastrosplenic ligament trium between the ventral abdominal between the stomach and the spleen and wall and the liver forms falciform (2) lienorenal ligament between the spleen ligament. and the kidney (Fig. 11.5). Stomach Aorta Ventral mesentery Dorsal mesentery Level of section b Liver Level of section c Spleen Falciform ligament Celiac artery Dorsal pancreatic bud Ventral pancreatic bud a Kidney Stomach Spleen Liver Aorta Dorsal mesentery Liver Kidney b Falciform Lienorenal ligament lgament Hepatogastric ligament Gastrosplenic ligament c Fig. 11.5 Illustration showing the fate of ventral and dorsal mesogastrium. (a) Sagittal section. (b, c) Transverse sections. Development of Gastrointestinal Tract 111 Anomaly embedded in the tail of the pancreas or in the gastrosplenic ligament. Congenital Hypertrophic Pyloric Stenosis: It occurs with the frequency of 1 in 150 male infants and 1 in 750 female infants, that is, Development of the the condition is five times more frequent in males. It presents with marked thickening at Duodenum pyloric end of the stomach. It is due to the hypertrophy of circular musculature and to It is of dual origin, that is, it is derived from some extent even longitudinal muscle. This both the foregut and the midgut. In the fourth causes marked stenosis (narrowing) of the week, duodenum begins to develop from the pyloric canal leading to obstruction to the caudal part of the foregut and the cranial part passage of food. Infants with this condition of the midgut. This gives rise to the lining have projectile vomiting. There is a possi­ epithelium and the glands. The connective bility of some genetic factor responsible for tissue and the musculature develop from the it, since it is seen with high frequency in both splanchnic mesenchyme surrounding the members of the monozygotic twin pair. The primitive gut. number of the autonomic ganglion cells in The junction of the two (developmen­ pyloric region in this condition is remarkably tally different) parts of the duodenum is reduced. marked by the opening of the bile duct. As these parts grow rapidly, the duodenum forms a “C­shaped” loop projecting ventrally Development of the (Fig. 11.6). Spleen Rotation of the Duodenum The spleen is derived from the differentia­ tion of the mesenchymal cells between the With the rotation of the stomach through 90 two layers of the dorsal mesogastrium. These degrees, the duodenal loop rotates onto the mesenchymal cells form the capsule, the right side. It soon becomes retroperitoneal­ connective tissue, and the parenchyma of the ized by fusion and subsequent disappearance spleen. Its development begins around the of the peritoneum (visceral and parietal) fifth week and is nearly complete during the on the back of the duodenum.