Review of Early Embryologic Development

Blastocyst and bilaminar disc

The morula (ball of cells) undergoes a process called blastulation, in which a cavity begins to form. The cells then begin differentiating into outer and inner cell masses.

• Outer cell mass → trophoblast → placenta Placenta The placenta consists of a fetal side and a maternal side, and it provides a vascular communication between the mother and the fetus. This communication allows the mother to provide nutrients to the fetus and allows for removal of waste products from fetal blood. Placenta, Umbilical Cord, and Amniotic Cavity and membranes
• Inner cell mass → embryoblast → bilaminar disc:
  • Epiblast
  • Hypoblast
• Amniotic sac: a cavity of fluid that develops “above” the epiblast (between epiblast and trophoblast)
• Primitive yolk sac: 
  • A cavity that forms “below” the hypoblast 
  • Important in GI development

Trilaminar disc

The bilaminar disc undergoes a process called gastrulation Gastrulation Both gastrulation and neurulation are critical events that occur during the 3rd week of embryonic development. Gastrulation is the process by which the bilaminar disc differentiates into a trilaminar disc, made up of the 3 primary germ layers: the ectoderm, mesoderm, and endoderm. Gastrulation and Neurulation to form the trilaminar disc. There are 3 layers of the trilaminar disc:

• Ectoderm (continuous with the amnion)
• Mesoderm:
  • Paraxial mesoderm
  • Intermediate mesoderm
  • Lateral plate mesoderm (LPM): 
    • Somatic layer of the LPM
    • Splanchnic layer of the LPM
  • Extraembryonic mesoderm:
    • Surrounds the amniotic cavity → continuous with somatic LPM
    • Surrounds the yolk sac → continuous with the splanchnic LPM
• Endoderm 
  • Embryonic endoderm (usually just called the endoderm) → becomes the primitive gut tube
  • Extraembryonic endoderm → lines the yolk sac
  • Secondary yolk sac: the cavity between embryonic and extraembryonic endoderm
• Folding of the trilaminar disc (folds in 2 directions):
  • Lateral folding: 
    • Creates a cylindrical structure surrounded by ectoderm and the amniotic cavity
    • Creates the primitive gut tube internally from endoderm
  • Cranial–caudal folding: 
    • Creates a cranial end and a caudal end (embryo becomes “bean-shaped”)

Forces the yolk sac farther from the body.→ The elongating stalk connecting the yolk sac to the gut tube is the vitelline duct.

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Obliteration of the vitelline duct and yolk sac

• As the embryo folds, the yolk sac is pushed farther and farther away from the body.
• Vitelline duct: elongating stalk that connects the midgut to the yolk sac as it is pushed away
• Growth of the amniotic cavity around weeks 4–6:
  • The amniotic cavity starts on the dorsal side of the embryo 
    • Grows and extends around the cranial and caudal ends of the embryo 
    • Edges of the growing cavity meet on the ventral side at the abdomen → pinch off the yolk sac/obliterate the vitelline duct
• Clinical relevance: Failure of the vitelline duct to obliterate results in Meckel diverticulum:
  • A true diverticulum (contains all layers of the bowel wall) 
  • Arises from the antimesenteric surface of the middle-to-distal ileum, anchoring it to the anterior abdominal wall Anterior abdominal wall The anterior abdominal wall is anatomically delineated as a hexagonal area defined superiorly by the xiphoid process, laterally by the midaxillary lines, and inferiorly by the pubic symphysis. Anterior Abdominal Wall.
  • May lead to fistula, volvulus Volvulus A volvulus is the twisting or axial rotation of a portion of the bowel around its mesentery. The most common site of volvulus in adults is the colon; most frequently the sigmoid volvulus. Patients typically present with symptoms of bowel obstruction such as abdominal pain, distension, vomiting, and constipation/obstipation. Volvulus, small bowel obstruction Small Bowel Obstruction Small bowel obstruction (SBO) is an interruption of the flow of the intraluminal contents through the small intestine, and is classified as mechanical (due to physical blockage) or functional (due to disruption of normal motility). The most common cause of SBO in the Western countries is post-surgical adhesions. Small bowel obstruction typically presents with nausea, vomiting, abdominal pain, distention, constipation, and/or obstipation. Small Bowel Obstruction, and/or necrosis

Foregut Derivatives, Omenta, and Spleen

Esophagus

Separation from the respiratory system:

• Lung bud (respiratory diverticulum): 
  • Buds off of the ventral side of the foregut around week 4
  • Simultaneously grows out (ventrally) and down (caudally)
  • Includes both endoderm and surrounding splanchnic LPM
• Tracheoesophageal groove (or ridge):
  • As the lung bud grows out and down, the tracheoesophageal groove appears as lateral indentations between the new lung bud and the foregut.
  • The grooves/ridges move in medially, pinching off the lung bud, and forming the tracheoesophageal septum.
• The tracheoesophageal septum creates 2 separate tubes:
  • Esophagus (posteriorly, from the original foregut)
  • Trachea Trachea The trachea is a tubular structure that forms part of the lower respiratory tract. The trachea is continuous superiorly with the larynx and inferiorly becomes the bronchial tree within the lungs. The trachea consists of a support frame of semicircular, or C-shaped, rings made out of hyaline cartilage and reinforced by collagenous connective tissue. Trachea (anteriorly, from the lung bud)
• Clinical relevance: 
  • Tracheoesophageal fistula Tracheoesophageal fistula Tracheoesophageal fistula is an abnormal connection between the trachea and esophagus. Esophageal Atresia and Tracheoesophageal Fistula (TEF): occurs when the tracheoesophageal grooves fail to fully close in the midline 
  • Esophageal atresia Esophageal atresia Esophageal atresia is a congenital anomaly in which the upper esophagus is separated from the lower esophagus and ends in a blind pouch. The condition may be isolated or associated with tracheoesophageal fistula, which is an abnormal connection between the trachea and esophagus. Esophageal Atresia and Tracheoesophageal Fistula: portions of the esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus fail to form; often coexists with TEF

Growth and descent:

• Esophagus lengthens and descends together with the heart and lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs
• Completes development by 7th week

Stomach

• Development begins around the 4th week
• Fusiform dilation of the foregut: site of primordial stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach
• The lengthening esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus places the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach below the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm
• Posterior wall grows more quickly than anterior wall → develops a C shape
  • Posterior wall → greater curvature
  • Anterior wall → lesser curvature
• 90-degree rotation clockwise around longitudinal axis:
  • Greater curvature (dorsal):
    • Rotates anteriorly and to the left
    • Left vagus nerve innervates anterior wall
  • Lesser curvature (ventral):
    • Rotates posteriorly and to the right
    • Right vagus nerve innervates posterior wall
• Smaller rotation clockwise around the anteroposterior axis:
  • Cardiac portion of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach moves down and to the left
  • Pyloric portion moves up and to the right

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Omenta

The greater and lesser omenta are formed from the dorsal and ventral mesogastrium (of mesodermal origin). As they rotate with the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach, they create the greater and lesser sacs.

Dorsal mesogastrium:

• Suspends stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach from the dorsal wall
• Originally located in the median plane
• Moved to the left during 90-degree longitudinal rotation
• Creates a space posterior to the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach called the lesser sac (i.e., omental bursa)
• Forms several important structures:
  • After rotation of the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach, bulges down to form the greater omentum
  • Gastrosplenic ligament: connects the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach and spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen
  • Splenorenal ligament: connects the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen to the posterior abdominal wall (near the kidney)
• Anterior to the greater omentum is the greater sac
• Structures developing within the dorsal mesogastrium:
  • Spleen
  • Pancreas

Ventral mesogastrium:

• Attached to the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach, duodenum, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver, and ventral abdominal wall
• Originally located in the median plane
• Moved to the right during 90-degree longitudinal rotation 
• Closes off the lesser sac between the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
• Forms 2 primary structures:
  • Lesser omentum: connects the stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach and liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver
  • Falciform ligament: connects the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver and the anterior abdominal wall Anterior abdominal wall The anterior abdominal wall is anatomically delineated as a hexagonal area defined superiorly by the xiphoid process, laterally by the midaxillary lines, and inferiorly by the pubic symphysis. Anterior Abdominal Wall
• Structures developing within the ventral mesogastrium:
  • Liver
  • Gallbladder
  • Bile ducts

Duodenum

• Development begins in the 4th week
• Above the ampulla of Vater: derived from caudal part of the foregut → supplied by the celiac artery
• Below the ampulla of Vater: derived from cranial part of the midgut → supplied by SMA SMA Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy (SMA)
• Elongates and forms C-shaped loop
• Joins together with the developing pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas attached to the posterior body wall
• Duodenal obliteration and recanalization:
  • Week 5: rapid cell proliferation in its walls leads to complete obstruction of the duodenal lumen
  • By the end of week 8: 
    • Vacuoles form within the duodenum 
    • Vacuoles grow and merge → lumen recanalization
  • Clinical relevance: failure of the lumen to fully recanalize results in either:
    • Duodenal stenosis: narrowing of the duodenum
    • Duodenal atresia: a complete obstruction persists; presents with bilious emesis and a double-bubble sign on radiography

Liver and biliary ducts

• Development begins in the 3rd‒4th week
• Appears from the caudal portion of the foregut as the hepatic diverticulum, which goes on to form the:
  • Liver (endoderm differentiates into hepatocytes)
  • Intrahepatic ducts
  • Extrahepatic portions of the hepatic ducts
• As the hepatic diverticulum enlarges, the connection to the duodenum narrows → common bile duct
• A smaller bud grows off the caudal side of the hepatic diverticulum:
  • Forms the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract
  • Connection between the caudal bud and the gallbladder Gallbladder The gallbladder is a pear-shaped sac, located directly beneath the liver, that sits on top of the superior part of the duodenum. The primary functions of the gallbladder include concentrating and storing up to 50 mL of bile. Gallbladder and Biliary Tract → cystic duct 
• The hepatic diverticulum grows into the ventral mesogastrium.
• Weeks 5–9: 
  • Hematopoietic stem cells (mesodermal origin) migrate into the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver:
    • Hematopoiesis begins 
    • Liver is the primary site of hematopoiesis up until about 28 weeks, when the primary job is taken over by the bone marrow Bone marrow Bone marrow, the primary site of hematopoiesis, is found in the cavities of cancellous bones and the medullary canals of long bones. There are 2 types: red marrow (hematopoietic with abundant blood cells) and yellow marrow (predominantly filled with adipocytes). Composition of Bone Marrow.
  • Synthesis of bile acid 
• Week 12: beginning of bile secretion by hepatocytes

Pancreas

• Development begins in the 4th week
• Develops primarily from a dorsal pancreatic bud off the foregut:
  • Accessory pancreatic duct
  • Part of the pancreatic head
  • Body 
  • Tail of the pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas
• A smaller ventral pancreatic bud contributes to the: 
  • Pancreatic head
  • Uncinate process
  • Main pancreatic duct
• Both endocrine and exocrine cells arise from the pluripotent endoderm-derived cells of the pancreatic bud
• Week 7: main pancreatic duct and accessory pancreatic ducts fuse
• By week 13: alpha, beta, and delta cells present in islets

Spleen

• Development begins in the 5th week
• Derived from mesenchymal cells (i.e., from mesoderm, not the endoderm-derived foregut)
• Forms from mesenchymal buds off the dorsal mesogastrium
• Buds fuse together, forming the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen.
• Lobulates during fetal life; lobules disappear before birth.
• Develops within the dorsal mesogastrium
• Supplied by celiac artery

Midgut and Hindgut Derivatives

The midgut develops into the lining of the GI tract from the distal duodenum (below the ampulla of Vater) to the midtransverse colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix. The hindgut develops into the GI tract from the distal ⅓ of the transverse colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix through the anus.

Midgut milestones

• Cranial portion: grows rapidly and forms small intestinal loop
• Develops cecal swelling:
  • Forms the cecum and appendix
  • Unequal growth of cecal walls → appendix enters the cecum medially
• Week 5: obliteration of the vitelline duct (yolk sac is pinched off from the midgut)
• Week 6: physiologic herniation of the midgut through the umbilicus
  • The midgut naturally herniates through the umbilical ring.
  • Creates more space within the embryo for the the developing abdominal organs (especially the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver)
• Weeks 6–10: 
  • Rapid growth of the midgut occurs outside the embryo
  • Rotation:
    • Midgut rotates 270 degrees counterclockwise around SMA SMA Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy (SMA).
    • Pulls the small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine into mature anatomic position: jejunum begins in the LUQ 
    • Pulls the large intestine Large intestine The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix into its mature anatomic position: upside-down U shape surrounding the small intestines
• Week 10: midgut returns to the abdominal cavity
  • Growing abdominal cavity creates enough space for the developing midgut
  • Clinical relevance: Failure of the midgut to reenter the abdomen results in an omphalocele Omphalocele Omphalocele is a congenital anterior abdominal wall defect in which the intestines are covered by peritoneum and amniotic membranes. The condition results from the failure of the midgut to return to the abdominal cavity by 10 weeks' gestation. Omphalocele (a congenital anterior abdominal wall Anterior abdominal wall The anterior abdominal wall is anatomically delineated as a hexagonal area defined superiorly by the xiphoid process, laterally by the midaxillary lines, and inferiorly by the pubic symphysis. Anterior Abdominal Wall defect in which the intestines are covered by peritoneum Peritoneum The peritoneum is a serous membrane lining the abdominopelvic cavity. This lining is formed by connective tissue and originates from the mesoderm. The membrane lines both the abdominal walls (as parietal peritoneum) and all of the visceral organs (as visceral peritoneum). Peritoneum and Retroperitoneum and amniotic membranes).

Hindgut milestones

The hindgut develops simultaneously and in close association with the urogenital system.

• Cloaca: 
  • Distal portion of the hindgut
  • Adjacent to the “outside” of the developing embryo at the cloacal membrane, which:
    • Area where endoderm and ectoderm met at the ends of the primitive gut tube
    • Ultimately ruptures, becoming the anus
  • Early in development, empties into a drainage tube called the allantois 
• Allantois:
  • Drains both gut tube and developing urinary system early 
  • Travels through umbilical cord 
  • Called the urachus later in development
  • Ultimately obliterates, becoming the median umbilical ligament along the internal anterior abdominal wall Anterior abdominal wall The anterior abdominal wall is anatomically delineated as a hexagonal area defined superiorly by the xiphoid process, laterally by the midaxillary lines, and inferiorly by the pubic symphysis. Anterior Abdominal Wall
  • Clinical relevance: incomplete obliteration can lead to a urachal fistula (infants may leak urine from the umbilicus at birth)
• Weeks 4‒7: cloaca divided by a growing urorectal septum:
  • Starts at the superior/proximal portion of the cloaca → grows distally until it reaches the outside of the body, where it becomes the perineal body
  • Separates the cloaca into 2 structures:
    • Urogenital sinus (anterior/superior): connects to the ureters; develops into the bladder, prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands (males), and urethra
    • Anal canal (posterior/inferior)
  • Clinical relevance: Failure of the anorectal septum to completely divide the cloaca can result in fistulas between the urogenital system and the anorectum.
• Anal pit:
  • Invagination of the ectoderm
  • Grows toward the anal canal
  • Pectinate line: 
    • The point where endoderm (proximal) and ectoderm (distal) of the anal canal meet
    • Marks the prior location of the cloacal membrane 
  • Clinical relevance:
    • Imperforate anus: failure of the cloacal membrane to rupture
    • Anal atresia: failure of the anal pit to form/meet rectum; more complicated repair because there are no sphincter muscles
• Hindgut/endoderm-derived: proximal ⅔ of the anal canal, lined by columnar epithelial cells
• Ectoderm-derived: distal ⅓ of the anal canal, lined by stratified squamous epithelial cells
• Hindgut is supplied by the IMA