LESSON 6 DEVELOPMENT OF THE DIGESTIVE SYSTEM Objectives By the end of this lesson, you should be able to: - 1. List divisions of the primitive gut 2. List derivatives of pharyngeal gut 3. List the derivatives of the foregut 4. Describe the development of the Liver, biliary system & the pancreas 5. List the derivatives of the Midgut 6. List the derivatives of the Hindgut 7. Describe the divisions of the cloaca 8. Describe the development of the serous body cavities 9. Describe the origin of the diaphragm FERTILIZATION AND IMPLANTATION Implantation

1. Decidua capsularis 2. Uterine wall 3. Uterine cavity 4. Placenta 5. Decidua parietalis 6. Decidua basalis 7. Chorion leave 8. Embryo 9. Connecting stalk 10. Yolk sac 11. Chorion frondosum 12. Amnion 13. Chorionic cavity 14. Amniotic cavity Fertilization, implantation and yolk sac development Gastrulation

Gastrulation – the process of establishment of overall body plan and general axis. The process involves migration of cells forming the primitive streak/embryonic disc (epiblast & hypoblast) through a process epithelial to mesenchymal transition. The results of the migration of cells is the formation of primitive germ layers – Endoderm, Mesoderm and Ectoderm Gastrulation INTRODUCTION • The primitive gut forms during the 4th week of the development as a result of cephalocaudal and lateral folding of the embryo. • This endoderm lined cavity is incorporated into the embryo, while the yolk sac and the allantois remain temporarily outside the embryo. • The endoderm of the primitive gut gives rise to the epithelium and glands of the digestive tract. • The muscular and fibrous elements of the digestive tract are derived from the splanchnic mesoderm. • The epithelium at the cranial and caudal extremities of the digestive tract is derived from the ectoderm of the stomodeum and the proctodeum (anal pit). Formation of the gut tube 1. Foregut 2. Hindgut 3. Midgut 4. Central nervous system 5. Tracheobronchial diverticulum 6. Heart 7. Liver bud 8. Buccopharyngeal membrane 9. Vitelline duct 10. Allantois 11. Cloacal membrane Formation of the primitive gut 1. Yolk sac 2. Surface ectoderm 3. Amniotic cavity 4. Neural groove 5. Splanchnic mesoderm 6. Somatic mesoderm Formation of the ventral abdominal wall 1.Yolk sac 2. Surface ectoderm 3. Amniotic cavity 4. Neural tube 5. Splanchnic mesoderm 6. Somatic mesoderm Formation of the ventral abdominal wall 1. Gut endoderm 2. Intraembryonic coelomic cavity 3. Amniotic cavity 4. Dorsal mesentery 5. Splanchnic mesoderm 6. Somatic mesoderm 7. Neural tube DEVELOPMENT OF THE PRIMITIVE GUT • The primitive gut is divided into four parts: – a) the pharyngeal gut which extends from the buccopharyngeal (oropharyngeal) membrane to the respiratory (tracheobronchial) diverticulum – b) the foregut, extending from the tracheobronchial diverticulum to the liver outgrowth – c) the midgut, extending from the liver outgrowth to the junction of the right two thirds and left one third of the transverse colon in the adult (posterior intestinal porta) – d) the hindgut, extending from the posterior intestinal porta to the cloacal membrane • The liver, biliary apparatus, pancreas and the respiratory system arise as diverticula from the foregut. • Along the entire length, the intestinal tube is suspended from the dorsal body wall by a dorsal mesentery. • Along the segment of its length, it is attached to the ventral body wall by a ventral mesentery. 1.Foregut 2. Stomach 3. Hindgut 4. Midgut 5. Pharyngeal gut 6. Esophagus 7. Tracheobronchial diverticulum 8. Buccopharyngeal membrane 9. Cloacal membrane 10. Stomodeum 11. Cloaca 12. Gallbladder 13. Liver 14. Pancreas 15. Vitelline duct 16. Allantois FOREGUT

• The derivatives of the foregut are the lower respiratory system, esophagus, stomach, duodenum proximal to the biliary tract, liver, pancreas, biliary tract and gallblader. OESOPHAGUS • In the 4th developmental week, a small diverticulum appears at the ventral wall of the foregut - the respiratory (tracheobronchial) diverticulum. • It becomes gradually separated from the foregut by the esophagotracheal septum. • Initially very short esophagus lengthens rapidly. The proliferation of esophageal epithelium almost obliterates the lumen, but the recanalization of the esophagus occurs by the end of the 8th week. Formation of the esophagus 1. Respiratory diverticulum 2. Foregut 3. Esophagotracheal septum Formation of the esophagus 1. Pharynx 2. Trachea 3. Esophagus 4. Lung buds STOMACH • The stomach appears as a fusiform dilation of the foregut in the 4th week of development. • The dorsal border grows faster than the ventral border, thus producing the greater curvature. • The stomach rotates along the longitudinal and antero- posterior axis. • The rotation of the stomach along the longitudinal axis causes its left side to face anteriorly, and its right side posteriorly. • The stomach is attached to the dorsal and ventral body wall by the dorsal and ventral mesogatrium. • During rotation, the dorsal mesogastrium is pulled to the left, forming the omental bursa. 1. Liver 2. Stomach 3. Spleen 4. Pancreas 5. Adrenal gland 6. Aorta 7. Dorsal mesogastrium 8. Omental bursa 9. Falciform ligament 10. Lesser omentum Stomach and dorsal mesentery • The dorsal mesogastrium extends tremendously as a double-layered flap of the mesentery, the greater omentum, which lies over the intestine. • As the spleen forms in the dorsal mesogastrium, the lienorenal and gastrolienal ligaments develop as remnants or dorsal mesogastrium. • The ventral mesogastrium attaches the lower esophagus, stomach and proximal duodenum to the ventral body wall. • Growth of the liver causes the formation of the lesser omentum and falciform ligament in the ventral mesogastrium. 1. Liver 2. Stomach 3. Spleen 4. Pancreas 5. Adrenal gland 6. Aorta 7. Lesser omentum 8. Lienorenal ligament 9. Gastrolienal ligament 10. Falciform ligament 11. Parietal peritoneum SPLEEN • The spleen is a lymphatic organ which appears during the 5th developmental week as a focus of mesenchymal proliferation between the layers of the dorsal mesogastrium. • As the stomach rotates, the left part of the dorsal mesogastrium comprises the gastrolineal and lienorenal ligaments. • The mesenchymal cells differentiate into the parenchymal cells, connective tissue and the surface capsule. • The spleen functions as a hematopoietic center until late fetal life. 1. Liver 2. Stomach 3. Spleen 4. Pancreas 5. Adrenal gland 6. Aorta 7. Dorsal mesogastrium 8. Omental bursa 9. Falciform ligament 10. Lesser omentum Spleen and dorsal mesentery 1. Liver 2. Stomach 3. Spleen 4. Pancreas 5. Adrenal gland 6. Aorta 7. Lesser omentum 8. Lienorenal ligament 9. Gastrolienal ligament 10. Falciform ligament 11. Parietal peritoneum DUODENUM

• The duodenum develops from the caudal portion of the foregut and cranial portion of the midgut. • The entrance of the bile duct into the duodenum lies just proximal to their junction. • The loop of the duodenum rotates to the right and comes to lie retroperitoneally. • The duodenal epithelium grows rapidly and temporarily obliterates the lumen of the gut tube. 1. Dorsal mesoduodenum 2. Pancreas 3. Duodenum 4. Parietal peritoneum 5. Aorta 6. Adrenal gland 1. Dorsal mesoduodenum 2. Pancreas 3. Duodenum 4. Parietal peritoneum 5. Aorta 6. Adrenal gland LIVER AND BILIARY APPARATUS • The liver, gallbladder and the biliary duct system arise as a bud of the endodermal epithelium at the distal end of the foregut. • The hepatic diverticulum (liver bud) grows into the septum transversum. • Septum transversum is the mesodermal plate between the pericardial cavity and the stalk of the yolk sac. • Cranial part of the septum transversum forms the tendinous portion of diaphragm, while its caudal part contributes to the ventral mesogastrium. • The large part of the liver bud forms the parenchyme of the liver and billiary apparatus. • The fibrous, hemopoietic tissue and Kupffer cells derive from the mesenchyme of the septum transversum. • A small caudal portion of the liver bud expands to form gallbladder and bile duct. 1. Esophagus 2. Hindgut 3. Stomach 4. Tracheobronchial diverticulum 5. Duodenum 6. Midgut loop 7. Septum transversum 8. Cloaca 9. Gallbladder 10. Liver 11. Cloacal membrane 12. Pancreas 13. Heart 14. Ventral mesogastrium 15. Dorsal mesogastrium Development of the liver and pancreas 1. Liver bud 2. Stomach 3. Gallbladder 4. Ventral pancreatic bud 5. Dorsal pancreatic bud PANCREAS • The pancreas develops from two separate endodermal duodenal diverticula, the dorsal and ventral pancreatic bud. • When the duodenum rotates, the ventral bud fuses with the dorsal bud. • The ventral bud forms the main pancreatic duct, uncinate process and part of the head of the pancreas, while the remaining part of the gland develops from the dorsal bud. Development of the liver and pancreas 1. Liver 2.Dorsal pancreatic bud 3. Gall bladder 4.Ventral pancreatic bud 5. Cystic duct 6. Hepatic duct 7. Common bile duct Development of the liver and pancreas 1. Stomach 2. Gallbladder 3. Cystic duct 4. Hepatic duct 5. Bile duct 6. Pancreas 7. Accessory pancreatic duct 8. Main pancreatic duct 9. Ventral pancreatic duct MIDGUT • The derivatives of the midgut are: most of the duodenum, small intestine, cecum, vermiform appendix, ascending colon and right two thirds of the transverse colon. • The wide communication of the midgut and the yolk sac is gradually reduced to the narrow yolk stalk (vitelline duct). • Rapid elongation of the midgut and its mesentery results in the formation of the midgut loop which projects into the umbilical cord (physiological umbilical herniation). • The cephalic limb of the loop develops into the duodenum, jejunum and part of the ileum, while the caudal limb gives rise to the rest of the midgut derivatives. • The midgut loop rotates 270º counterclockwise around the axis formed by the superior mesenteric artery. 1. Vitelline duct 2. Superior mesenteric artery 3. Stomach 4. Duodenum 5. Cephalic limb of the loop 6. Caudal limb of the loop 1. Vitelline duct 2. Superior mesenteric artery 3. Stomach 4. Duodenum 5. Transverse colon 6. Small intestine 7. Ceacal bud MIDGUT LOOP • During the 10th week, the intestines return to the abdomen. • The ceacal diverticulum (the primordium of the cecum and vermiform appendix) is first located in the upper right quadrant of the abdomen, then descends into the right iliac fossa. • As the ascending colon assumes its final position, its mesentery is pressed against the peritoneum of the posterior abdominal wall and is permanently anchored in retroperitoneal position. • While its mesentery disappears, the mesentery of other derivatives of the midgut loop remains. • During the development, the alimentary canal goes through a transient solid state, followed by a recanalization. 1. Vitelline duct 2. Small intestine 3. Stomach 4. Duodenum 5. Transverse colon 6. Ceacal bud 1. Hepatic flexture 2. Stomach 3. Duodenum 4. Transverse colon 5. Ascending colon 6. Descending colon 7. Sigmoid 8. Cecum 9. Appendix 10. Amall intestine HINDGUT • The hindgut extends from the midgut to the cloacal membrane. • It gives rise to the distal third of the transverse colon, descending colon, sigmoid, rectum and the upper part of the anal canal. • The teminal portion of the hindgut enters into the cloaca covered by the cloacal membrane. • The growth of the urorectal septum divides the cloaca into the primitive urogenital sinus anteriorly and the anorectal canal posteriorly. • By the end of the 6th week, the urorectal septum reaches the cloacal membrane, dividing it into the urogenital and anal membranes. • The mesenchymal swelling around the anal membrane forms the proctodeum (anal pit). • In the 9th week, the anal membrane ruptures. • The upper part of the anal canal is endodermal in origin, while the lower third is of the ectodermal origin. Division of the cloaca 1. Urogenital ridge 2. Genital ridge 3. Mesonephric duct 4. Mesonephros 5. Gonad 6. Metanephric tissue 7. Ureter 8. Cloacal membrane 9. Cloaca 10. Allantois 11. Urorectal septum Division of the cloaca 1. Mesonephric duct 2. Mesonephros 3. Gonad 4. Metanephros 5. Ureter 6. Cloacal membrane 7. Cloaca 8. Urorectal septum 9. Urogenital sinus 10. Anorectal canal 11. Tail 1. Ureter 2. Metanephros 3. Gonad 4. Mesonephric duct 5. Anal membrane 6. Urogenital membrane 7. Perineal body 8. Bladder 9. Rectum SEROUS MEMBRANES AND BODY CAVITIES • The lateral plates of the intraembryonic mesoderm form the somatic (parietal) mesoderm layer (future parietal serous membrane) and splanchnic (visceral) mesoderm layer (future visceral serous membrane). • They border the intraembryonic coelom which is gradually divided into peritoneal, pleural and pericardial cavity. • The septum transversum, a thick plate of the mesodermal tissue between the thoracic cavity and the stalk of the yolk sac, incompletely separates the thoracic and peritoneal cavities ventrally, thus separating the thoracic and abdominal cavities. • Pericardioperitoneal canals, on each side of the foregut, leave openings between the two cavities. 1. Lung bud 2. Heart 3. Common cardinal vein 4. Aorta 5. Pleuropericardial membrane 6. Pericardial cavity 1. Pleural cavity 2. Lung 3. Visceral pleura 4. Aorta 5. Pericardial cavity 6. Parietal pleura 7. Superior vena cava 8. Fibrous pericardium 9. Heart 1. Esophagus 2. Hindgut 3. Stomach 4. Tracheobronchial diverticulum 5. Duodenum 6. Midgut loop 7. Septum transversum 8. Cloaca 9. Gallbladder 10. Liver 11. Cloacal membrane 12. Pancreas 13. Heart 14. Ventral mesogastrium 15. Dorsal mesogastrium • With the expansion of the lungs, the mesoderm of the body wall is split into the definitive wall of the thorax and the pleuropericardial membrane. • When the pleuropericardial membranes fuse with each other and the root of the lungs they divide the thoracic cavity into the pericardial cavity and the pleural cavity. • During further development, the pleuroperitoneal membranes extend in ventro-medial direction and fuse with the mesentery of the esophagus and septum transversum. • Muscular ingrowth from the body wall penetrate the membranes to form the muscular part of the diaphragm. • The diaphragm is formed of the septum transversum, two pleuroperitoneal membranes, muscular component from the body walls, and mesentery of the esophagus. Development of the diaphragm 1. Pleuroperitoneal membrane 2. Septum transversum 3. Muscular part of diaphragm 4. Mesentery of the esophagus 5. Inferior vena cava 6. Esophagus 7. Aorta 8. Body wall Conclusion Development of the primitive gut Pharyngeal gut Foregut Liver, biliary system & the pancreas Midgut Hindgut Divisions of the cloaca Serous body cavities diaphragm