Embryology of the Human Digestive System PPT PDF

EMBRYOLOGY OF THE HUMAN DIGESTIVE SYSTEM ANGELINE LLABRES CARL OWEN MADRONA —DMD 2—  REPORT TOPICS Divisions of the Gut Molecular tube regulation of liver Induction Molecular regulation of Gut Pancreas tube develo...

EMBRYOLOGY OF THE HUMAN DIGESTIVE SYSTEM ANGELINE LLABRES CARL OWEN MADRONA —DMD 2—  REPORT TOPICS Divisions of the Gut Molecular tube regulation of liver Induction Molecular regulation of Gut Pancreas tube development Midgut Mesenteries Hindgut Foregut  EMBRYOLOGY OF THE DIGESTIVE SYSTEM Germ tissues, the base of all tissues and organs, is formed during gastrulation. By week 2, the endoderm, mesoderm, and ectoderm is developed  The Primitive gut tube develops during week 3- DIVISIONS OF THE GUT TUBE 4 by incorporating the yolk sac during cranio- caudal and lateral folding of the embryo. Foregut gives rise to the esophagus, stomach, liver, gallbladder, bile ducts, pancreas and proximal duodenum. The midgut develops into the distal duodenum, jejunum, ileum, cecum, appendix, ascending colon, and proximal 2/3 of transverse colon. The hindgut becomes the distal 1/3 of the transverse colon, descending colon, sigmoid colon and the upper anal canal.  MOLECULAR REGULATION OF GUT TUBE DEVELOPMENT The concentration gradient of retinoic acid (RA) causes transcription factors, initiating the regional specification of the gut tube. RA from the pharynx has little to no exposure to RA; whereas RA from the colon with high exposure to RA SOX2 expression specifies the esophagus and stomach; PDX1 expression, the duodenum; CDXC, the small intestine; CDXA, the large intestine and rectum. Sonic hedgehog (SHH) expression initiates the epithelial- mesencymal interaction which is responsible for stabilizing the initial patterning  MESENTERY DEVELOPMENT Mesentery is a fan-shaped fold in the peritoneum that suspends the intestines and other abdominal organs from the posterior abdominal wall. It serves as a conduit for blood vessels, lymphatics, and nerves, providing support and allowing mobility within the abdominal cavity. Initially the foregut, midgut, and hindgut is attached to the posterior mesenchymal wall up until the 5th week, by which the connecting tissue narrows, shifting the attachment of the gut tube to the abdominal wall through the dorsal mesentery.  Dorsal mesentery is divided MESENTERY into regions: Dorsal mesogastrium,greater omentum, mesoduodenum, mesentery proper, mesocolon, mesoappendix, mesosigmoid, and mesorectum. Ventral mesentery Derived from mesenchyme of the septum transversum Divides into ventral meso- gastrium and falciform ligament as the liver grows into the septum FOREGUT foregut develops into the esophagus, stomach, liver, gallbladder, pancreas and the caudal portion of the duodenum ESOPHAGUS At week 4, the Respiratory diverticulum forms, which is then gradually partitioned by the tracheoesophageal septum, dividing the foregut into a ventral portion, the respiratory primordium, and the dorsal portion, the esophagus.  STOMACH During week 4 of development in the foregut begins, forming the fusiform dilation approximate to the respiratory diverticulum After a few weeks of growth in the esophageal region, evident appearance and positional changes is observed in the stomach caused by the 90 degree clockwise rotation around a longitudinal axis. This rotation also causes growth difference in the anterior and posterior portion, forming the lesser and greater curvature. STOMACH Dorsal mesogastrium attaches the stomach to the dorsal body wall; and the ventral mesogastrium to the ventral body wall. The mesoderm of ventral mesogastrium then becomes thinner as the liver grows into the region, forming the two parts of ventral mesentery: lesser omentum, falciform ligament. The free region of the falciform ligament contains the umbilical vein which is then destroyed and replaced by the round ligament of the liver. The free region of the lesser omentum thickens to form the portal pedicle which contains the bile duct, portal vein, and hepatic artery and also forms the roof of the epiploic foramen which connects the lesser sac to the greater sac. Ornamental bursa/ peritoneal sac is formed due to the rotation pulling the dorsal mesogastrium to the left, creating a space behind the stomach At the 5th week, the spleen premordium develops as a mesodermal proliferation The greater omentum is a double-layered sac developing from the down growth of dorsal premordium due to the rotation.  DOE S YO UR WHERE O M E FR OM ? LIVER C The liver starts as part of a tube in the embryo called the foregut, formed from a layer of cells called the endoderm. The endoderm is like the "blueprint" for many organs, including the liver.  ULATION OF LIVER MOLECULAR REG INDUCTION The liver develops from the foregut endoderm but requires specific molecular signals to initiate its development. Surrounding tissues, including ectoderm, mesoderm, and notochord, release inhibitors to suppress liver-specific gene expression across most of the foregut.  E SIGNALS INDUCTIV Fibroblast Growth Factor 2 (FGF2) They are secreted by the cardiac mesoderm and blood vessel- forming endothelial cells. It overrides inhibitory signals, initiating liver gene expression. Bone Morphogenetic Proteins (BMPs) Produced by the septum transversum, they prepare the endoderm to respond to FGF2 signals.  CELL DIFFERENTIATION Hepatocyte Nuclear Once the instructions from Factors those factors are received, (HNF3 and HNF4) cells in the liver field differentiate into both hepatocytes and biliary cell , a process partially regulated by Hepatocyte Nuclear Hepatocytes Biliary cells Factors (HNF3 and HNF4).  E D OE S YOU R WHER PANCR EA S CO ME FROM? The pancreas forms from two separate endodermal buds, dorsal and ventral. Dorsal Bud The first to form, located within the dorsal mesentery. Ventral Bud Develops near the bile duct and shifts during gut rotation to merge with the dorsal bud.  L CONTRIBUTIONS STRUCTURA Ventral Bud Dorsal Bud Forms the uncinate process and Forms the remaining pancreas, lower pancreatic head. including the body and tail. The ducts from both buds fuse to form the main pancreatic duct of Wirsung. The proximal part of the dorsal pancreatic duct may either persist as a small channel, known as the accessory pancreatic duct of Santorini.  R SIGNALS MOLECULA Sonic Hedgehog (SHH) FGF2 and Activin block SHH expression in the dorsal bud to allow pancreatic development. Pancreatic And Duodenal Homeobox 1 (PDX1) Gene Initiates pancreatic development. PAX4 and PAX6 Genes—determine endocrine cell types: PAX4 and PAX6: PAX6 Only Beta cells (insulin), delta cells Alpha cells (glucagon). (somatostatin), and gamma cells (pancreatic polypeptide).  ENDOCRINE DEVELOPMEN T 3rd Month of Fetal Life pancreatic islets (of Langerhans) develop from the parenchymatous pancreatic tissue 5th Month of Fetal Life The pancreas starts secreting insulin, glucagon, and somatostatin  MIDGUT DEVELOPM ENT The midgut extends from the bile duct to the junction of the transverse and descending colon, forming much of the small intestine and proximal large intestine.  KEY PROCESSES Formation of the Primary Intestinal Loop The rapid growth of the gut tube creates a U-shaped loop connected to the yolk sac via the vitelline duct. Cephalic Limb: Develops into the duodenum, jejunum, and part of the ileum. Caudal Limb: Forms the distal ileum, cecum, appendix, ascending colon, A. Primary intestinal loop before rotation [lateral view]. The superior and proximal transverse colon. mesenteric artery forms the axis ofthe loop. Arrow, counterclockwise rotation. B. Similar view as in [A] showing the primary intestinal loop after 90° counterclockwise rotation. The transverse colon passes in front of the duodenum.  PHY SIOLOGICAL HERNIATION During the 6th week of development, the midgut elongates rapidly Due to limited space in the abdominal cavity caused by liver expansion, the intestinal loops temporarily herniate into the umbilical cord. This process is known as physiological umbilical herniation.  ROTATION OF THE MIDGUT As the midgut herniates, it rotates counterclockwise around the superior mesenteric artery. The rotation totals 270° 90° occurring during herniation remaining 180° during the loops' return to the abdomen.  DEVELOPMENT HINDGUT The hindgut forms the distal transverse colon, descending colon, sigmoid colon, rectum, and upper anal canal. It also contributes to the internal lining of the bladder and urethra.  VELOPMENT CLOACAL DE The terminal portion of the hindgut ends in the cloaca, an endoderm-lined cavity involved in early development. This structure is divided by the urorectal septum into: Anorectal Canal: Becomes the rectum and upper anal canal. Urogenital Sinus: Develops into the bladder and urethra. Seventh week of Creates separate openings for development the anal canal and urogenital the cloacal membrane sinus. The point where the —a boundary between urorectal septum meets the endoderm and ruptured membrane forms the ectoderm—ruptures. perineal body. REFERENCES: Sadler, T. W., & Langman, J. (2024). Langman's medical embryology (14th ed.). Wolters Kluwer. Shin, D., & Monga, S. P. (2013). Cellular and molecular basis of liver development. Comprehensive Physiology, 3(2), 799–815. https://doi.org/10.1002/cphy.c120022 Pandol SJ. The Exocrine Pancreas. San Rafael (CA): Morgan & Claypool Life Sciences; 2010. Pancreatic Embryology and Development. Available from: https://www.ncbi.nlm.nih.gov/books/NBK54135/ Malone JC, Arbor TC, Shah AB. Embryology, Midgut. [Updated 2023 Mar 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK553156/  DM 103 THANK YOU FOR LISTENING!