Development of Digestive System

Most of the digestive system (except for the majority of the oral cavity and anal canal, and some of the salivary glands) develops from the primitive gut, which was created by the folding of the trilaminar embryonic disc to form the embryo proper during the 4th week. Formation of the primitive gut yields one of the principal features of the vertebrate body plan - a tube within a tube. Later development of the gut during the embryonic period (gut rotation and development of accessory glands and organs) will produce exceptions to another principal feature of the vertebrate body plan - bilateral symmetry. Another interesting feature of further development of the primitive gut is its cranial-to-caudal progression.

Formation of the Primitive Gut (week 4)

Germ layers and the presumptive primitive gut

• The mucosal epithelium and associated glands of the gastrointestinal tract develop from endoderm. Embryonic endoderm is formed in the 3rd week as the ventral layer of the trilaminar embryonic disc.
• The connective tissue, muscle and mesothelium are derived from splanchnic mesoderm. The lateral plate region of mesoderm can be distinguished in the fourth week. In the posterior (caudal) half of the embryo, the lateral plate mesoderm splits to form a dorsal somatic mesoderm and a ventral splanchnic mesoderm. Somatic mesoderm with the overlying ectoderm is called the somatopleure; and splanchnic mesoderm and endoderm, the splanchnopleure.
• The enteric nervous system develops from neural crest cells.
• In the older literature, the hypoblast of the bilaminar embryo was often called the "primitive endoderm". But as evidence accumulated that the embryonic endoderm is derived from the epiblast rather than the hypoblast, the term "primitive endoderm" fell into disfavor.

Formation of the primitive gut

Embryo formation by folding of the trilaminar embryo in the 4th week creates the primitive gut.

• Lateral folding of the splanchnopleure results in a midline tube along an anterior-posterior axis, and lateral folding of the somatopleure closes the body wall creating the periotoneum from trapped intra- and extra-embryonic coelom. Simultaneously, the connection between the primitive gut and the dorsal body wall thins to form a dorsal mesentery (and dorsal mesogastrium).
• Cranial folding of the embryo brings the anterior end of the embryonic disk down to the level of the distal end of the foregut, where it forms the septum transversum, and the prechordal plate to the cranial end of the primitive gut, where it forms the oropharyngeal (or buccopharyngeal) membrane. The septum transversum becomes the central tendon of the diaphragm and the ventral mesogastrium. After it is invaded by the liver bud, the ventral mesogastrium gives rise to the falciform ligament, capsule of the liver, and lesser omentum.
• Caudal folding of the embryo places a cloacal membrane at the terminal end of the primitive gut.

Divisions of the primitive gut

The primitive gut is divided into three regions (foregut, midgut and hindgut), initially by defining the midgut as the portion that is continuous with the umbilical vesicle ("yolk sac"). Later, the dividing lines between the regions are defined by the borders of the vascular territories of the celiac, and superior and inferior mesenteric arteries. These arteries are located in the dorsal mesogastrium, mesentery of the midgut and mesentery of the hindgut, respectively.

Sagittal section of embryo at about 4 weeks showing the primitive gut. Gray's Anatomy (1918) figure 977 (originally from His). Source: WikiMedia Commons

The abdomen of an embryo in the 6th week showing the alimentary system, mesentery, dorsal mesogastrium, and derivatives of the ventral mesogastrium (falciform ligament, capsule of the liver and lesser omentum). Gray's Anatomy (1918) figure 984 (originally from Kollmann). Source: WikiMedia Commons

Development of the alimentary system at about 4 weeks (A) and 5 weeks (B). Gray's Anatomy (1918) figure 982 (originally from His). Source: WikiMedia Commons

Alimentary system at about 6 weeks showing arterial supply. Gray's Anatomy (1918) figure 985 (originally from Toldt). Source: WikiMedia Commons

Development of the Foregut (weeks 4-7)

The foregut extends from the oropharyngeal membrane to (and includes) the hepatocystic diverticulum (liver bud). The foregut can be further divided into cranial and caudal regions.

Cranial foregut

The cranial foregut, or pharyngeal gut, extends from the oropharyngeal membrane to (and includes) the respiratory diverticulum (lung bud). The derivatives of the pharyngeal gut include part of mouth and tongue, pharynx, thyroid, parathyroid, thymus, lower respiratory tract, and lungs.
The pharyngeal gut and stomodeum both contribute to development of the mouth. The stomodeum is an ectodermal depression in the developing face that forms the primordial mouth. After the oropharyngeal membrane, which separates the stomodeum from the pharyngeal gut, ruptures in the 5th week, the stomodeum connects the amniotic cavity and the pharyngeal gut.

Pharyngeal ("branchial") arches appear during the 4th and 5th weeks on the ventral side of the pharyngeal gut. Each arch has cartilage, a cranial nerve, an aortic arch artery and muscle. Pharyngeal clefts and pouches are located between the arches. (See Pharyngeal Apparatus for more on the pharyngeal arches, clefts and pouches.)

At about 4 weeks, the respiratory diverticulum (or lung bud) appears. At the end of the embryonic period, the lungs are in a pseudoglandular phase in which pulmonary lobes and segments can be identified.

The respiratory diverticulum at about 5 weeks. Gray's Anatomy (1918) figure 948 (originally from His). Source: WikiMedia Commons.

The respiratory diverticulum at about 6 weeks. Gray's Anatomy (1918) figure 949 (originally from His). Source: WikiMedia Commons

The alimentary system at about 5 weeks (left) and at about 7 weeks (right). Gray's Anatomy (1918) figure 983 (originally from His). Source: WikiMedia Commons

Caudal foregut

The caudal foregut, sometimes simply called the foregut, begins after the respiratory diverticulum and extends to (and includes) the hepatocystic diverticulum. The derivatives of the caudal foregut include: esophagus, stomach, proximal duodenum, liver, gall bladder, hepatic and bile ducts, and pancreas.
At first very short, the esophagus lengthens both prenatally and postnatally.
At about 4 weeks, the stomach is a dilatation of the foregut. In the 5th week, the stomach rotates 90° around its longitudinal axis so that the original dorsal side becomes the left side. In the 6th week, the left side grows faster than the right, creating the greater and lesser curvatures. In the 7th week, further growth of the stomach gives the appearance of rotation around the dorsal-ventral axis, moving the distal foregut to the right.
The liver bud (hepatocystic diverticulum) appears at the distal end of the foregut at 4 weeks; the hepatic and cystic diverticula, hepatic sinusoids and dorsal pancreas, at 4 ½ weeks; and the ventral pancreas, at 5 weeks. At 6 weeks, the pancreatic components meet and fuse.

Abdomen of an embryo showing growth of the liver within the septum transversum during the 5th week. Gray's Anatomy (1918) figure 1088 (originally from His). Source: WikiMedia Commons

The ventral and dorsal pancreases approach each other during the 6th week. Gray's Anatomy (1918) figure 1101 (originally from His). Source: WikiMedia Commons

Fusion of the ventral and dorsal pancreases at about 6 weeks. Gray's Anatomy (1918) figure 1102 (originally from His). Source: WikiMedia Commons

Development of the Midgut (weeks 5-10)

The midgut is divided into two regions at the omphalo-enteric duct ("yolk stalk"): the cranial and caudal limbs. The derivatives of the cranial limb include the distal duodenum, jejunum, and proximal ileum. The derivatives of the caudal limb include the distal ileum, cecum, appendix, ascending colon, and proximal 2/3 of transverse colon.

Proliferation of epithelium in many places in the developing GI tract may narrow the lumen during the 2nd month. The duodenum may be occluded during the 5th and 6th weeks. Recanalization of the duodenum in the 7th week is by coalescence of extracellular vacuoles. Failure of recanalization of the duodenum is believed to be a cause of duodenal atresia.

The length of the midgut grows faster than that of the embryo, creating a gut "loop", with the omphalo-enteric (vitelline) duct at the apex. In the 6th week, the midgut enters the extraembryonic coelom of the developing umbilical cord (physiological umbilical herniation). At this time, the omphalo-enteric duct closes and the entire midgut loop rotates 90°. In the 10th week, the midgut returns to the abdomen, and rotates further (180° as measured at the apex of the loop).

After the midgut returns to the abdomen, there is shortening of some segments of the mesentery with fixation of three intestinal segments to the posterior abdominal wall. Fixation of the intestines results in most of the duodenum, pancreas, ascending colon and descending colon becoming secondarily retroperitoneal, and reduces the freedom of motion of the bowel, reducing the risk of volvulus and intestinal infarction.

The alimentary system at about 6 weeks showing the midgut loop. Gray's Anatomy (1918) figure 985 (originally from Toldt). Source: WikiMedia Commons

Human embryo in the 7th week showing the physiological umbilical herniation of the midgut into the extra-embryonic coelom (chorionic cavity remnant) within the developing umbilical cord. Note the midgut loop has rotated 90°.Gray's Anatomy (1918) figure 986 (originally from Mall). Source: WikiMedia Commons

The alimentary system showing completion of the midgut rotation following retraction of the midgut into the peritoneum in the 10th week. Gray's Anatomy (1918) figure 987. Source: WikiMedia Commons

The alimentary system showing the mature pattern of arrangement of the intestines, and superior and inferior mesenteric arteries. Gray's Anatomy (1918) figure 988 (originally from Jonnesco). Source: WikiMedia Commons

Development of the Hindgut (weeks 5-7)

The hindgut is the distal segment of the primitive gut from the junction with the midgut to the cloacal membrane. The distal end of the hindgut is called the cloaca. (In birds, reptiles and amphibians, the cloaca is the common "sewer" for excretions of the alimentary, urinary and genital systems.) Caudal to the cloaca, there is a temporary extension of the embryonic hindgut known as the tail gut (or postanal gut).
Derivatives of the hindgut include the distal 1/3 of the transverse colon, descending colon, sigmoid colon, rectum and anal canal above the pectinate line, urinary bladder, and proximal urethra.

Division of the cloaca starts with formation of a urorectal septum. The urorectal septum begins as mesoderm around the allantoic diverticulum that, as it grows (beginning in the 5th week), divides the cloaca into a ventral primitive urogenital sinus and a dorsal primitive anorectal canal. The cloacal membrane breaks down in the 7th week, before the urorectal septum reaches it.

Distal to the pectinate line (site of the former cloacal membrane), the epithelium of the anal canal is derived from ectoderm. This line also marks important changes in musculature, innervation, arterial supply and venous drainage.

The caudal end of a human embryo in the 5th week, showing the cloaca prior to growth of the urorectal septum. Note also the presence of the frequently overlooked tail (or postanal) gut. Gray's Anatomy (1918) figure 991 (originally from Keibel). Source: WikiMedia Commons

The cloaca at about 5 weeks, showing early growth of the urorectal septum. Gray's Anatomy (1918) figure 992 (originally from Keibel). Source: WikiMedia Commons

The caudal end of a human embryo at about 6 weeks, showing division of most of the cloaca. Note also the obliteration of the tail-gut. Gray's Anatomy (1918) figure 1116 (originally from Keibel). Source: WikiMedia Commons

The caudal end of a human fetus at about 9 weeks showing complete division of the cloaca, forming the primitive urogenital sinus and primitive anorectal canal. Gray's Anatomy (1918) figure 993 (originally from Keibel). Source: WikiMedia Commons

Selected Malformations of the Digestive System

• Anomalies of the foregut
  • Esophageal atresia and/or tracheoesophageal fistula
  • Pyloric stenosis
  • Anomalies of the extrahepatic biliary apparatus (e.g., extrahepatic biliary atresia)
  • Annular pancreas
• Anomalies of the intestines (midgut and hindgut)
  • Bowel atresias and stenoses (e.g., duodenal stenosis and atresia)
  • Cysts and intestinal duplications
  • Meckel's diverticulum and related anomalies (cyst, sinus, fistula)
  • Midgut rotation defects and defects of fixation
• Anomalies of the hindgut
  • Congenital intestinal aganglionosis (Hirschsprung disease or congenital megacolon)
  • Anorectal anomalies (stenosis, atresia, agenesis, fistulas)
• Other anomalies affecting the alimentary system
  • Body wall defects (omphalocele and gastroschisis)
  • Diaphragm defects (diaphragmatic hernias)

External Links

Human Developmental Anatomy Center (HDAC) of the National Museum of Health & Medicine

• O'Rahilly R & Müller F. Developmental Stages in Humans. Carnegie Institution of Washington, 1987.
  

Embryology.ch - an online course in embryology for medical students

Other Resources

O'Rahilly R and Müller F. Human Embryology & Teratology, 3rd Ed. New York: Wiley-Liss, 2001.