Gastrointestinal Tract Development

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Contents

Introduction

Gray0982a.jpg

The gastrointestinal tract (GIT) extending from the buccopharyngeal membrane to the cloacal membrane arises initially from the endoderm of the trilaminar embryo (week 2, 3). It later has contributions from all the germ cell layers.

During the 4th week the 3 distinct portions (fore-, mid- and hind-gut) extend the length of the embryo and will contribute different components of the GIT. The large mid-gut is generated by lateral embryonic folding which "pinches off" a pocket of the yolk sac, the 2 compartments continue to communicate through the vitelline duct. On this current page there is a brief developmental overview and stage 13/14 embryo overview.

The oral cavity (mouth) is formed following breakdown of the buccopharyngeal membrane (oropharyngeal or oral) and contributed to mainly by the pharynx lying within the pharyngeal arches. The opening of the GIT means that it contains amniotic fluid, which is also swallowed later in development.

From the oral cavity the next portion of the foregut is initially a single gastrointestinal (oesophagus) and respiratory (trachea) common tube, the pharynx which lies behind the heart. Note that the respiratory tract will form from a ventral bud arising at this level (More? Respiratory)

GIT Links: Introduction | Lecture - GIT | Endoderm | Stomach | Liver | Gall Bladder | Pancreas | Intestine | Tongue | Taste | Stage 13 | Stage 22 | Abnormalities | Movies | Postnatal | Milk | Tooth | Tongue | BGD Lecture | BGD Practical | Category:Gastrointestinal Tract
GIT Histology Links: Colon | Smooth Muscle Histology | Liver | Gall Bladder | Pancreas | Histology Stains | Histology | GIT Development

Some Recent Findings

Early endoderm development
  • Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver[1] In the developing human liver, three-dimensional reconstructions using multiple marker proteins confirmed that the human intrahepatic biliary tree forms through several developmental stages involving an initial transition of primitive hepatocytes into cholangiocytes shaping the ductal plate followed by a process of maturation and remodeling where the intrahepatic biliary tree develops through an asymmetrical form of cholangiocyte tubulogenesis. Liver Development
  • Endocrine Pancreas[2] "The transcription factor Pax6 functions in the specification and maintenance of the differentiated cell lineages in the endocrine pancreas. It has two DNA binding domains, the paired domain and the homeodomain, in addition to a C-terminal transactivation domain. The phenotype of Pax6-/- knockout mice suggests non-redundant functions of the transcription factor in the development of glucagon-expressing alpha-cells as this cell type is absent in the mutants."

Textbooks

  • Human Embryology Larson Chapter 9 p229-260
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Chapter 12 p271-302
  • Before We Are Born (5th ed.) Moore and Persaud Chapter 13 p255-287
  • Essentials of Human Embryology Larson Chapter 9 p123-146
  • Human Embryology Fitzgerald and Fitzgerald Chapter 19,20 p119-123

More? References | Online Textbooks | Historic Textbooks

Objectives

  • Understanding of germ layer contributions to the early gastrointestinal tract (GIT)
  • Understanding of the folding of the GIT
  • Understanding of three main GIT embryonic divisions
  • Understanding of associated organ development (liver, pancreas, spleen)
  • Brief understanding of mechanical changes (rotations) during GIT development
  • Brief understanding of gastrointestinal abnormalities

Germ Layer Contributions

  • Endoderm - epithelium and associated glands
  • Mesoderm (splanchnic) - mesentry, connective tissues, smooth muscle, blood vessels
  • Ectoderm (neural crest) - enteric nervous system (neural tube) - extrinsic innervation

Both endoderm and mesoderm will contribute to associated organs.

Gastrointestinal Tract Movies

GIT Cartoons
Mesoderm 001 icon.jpg
 ‎‎Week 3 Mesoderm
Page | Play
Endoderm 002 icon.jpg
 ‎‎Endoderm
Page | Play
Gastrointestinal tract growth 01 icon.jpg
 ‎‎Tract Growth
Page | Play
Stomach rotation 01 icon.jpg
 ‎‎Stomach Rotation
Page | Play
Lesser sac 01 icon.jpg
 ‎‎Lesser sac
Page | Play
Greater omentum 001 icon.jpg
 ‎‎Greater Omentum
Page | Play

3 GIT divisions

GIT blood supply.jpg
During the 4th week the 3 distinct portions (fore-, mid- and hind-gut) extend the length of the embryo and will contribute different components of the GIT. These 3 divisions are also later defined by the vascular (artery) supply to each of theses divisions.

The large mid-gut is generated by lateral embryonic folding which "pinches off" a pocket of the yolk sac, the 2 compartments continue to communicate through the vitelline duct.

The oral cavity (mouth) is formed following breakdown of the buccopharyngeal membrane (oropharyngeal, oral membrane) and contributed to mainly by the pharynx lying within the pharyngeal arches. The opening of the GIT means that it contains amniotic fluid, which is also swallowed later in development.

Foregut

Stage 11 foregut
From the oral cavity the next portion of the foregut is initially a single gastrointestinal (oesophagus) and respiratory (trachea) common tube, the pharynx which lies behind the heart. Note that the respiratory tract will form from a ventral bud arising at this level.
  • Oral cavity
  • Pharynx (esophagus, trachea)
  • Respiratory tract
  • Stomach

Midgut

midgut herniation

From beneath the stomach the initial portion of the small intestine, the duodenum, and the associated pancreas now lie.

Much of the midgut is herniated at the umbilicus external to the abdomen through development. A key step in development is the rotation of this midgut that must occur to place the GIT in the correct abdominal position with its associated mesentry. The GIT itself differentiates to form significantly different structures along its length: oesophagus, stomach, duodenum, jejunum, iliem (small intestine), colon (large intestine).

The mesentries of the GIT are generated from the common dorsal mesentry, with the ventral mesentry contributing to the lesser omentum and falciform ligament.

Hindgut

The distral transverse colon, descending colon, sigmoid colon, rectum and cloaca. The cloaca is the common urogenital sinus which will later become partitioned into an anterior urinary and posterior GIT rectal component.


Links: Intestine Development

Development Overview

GIT shown in green anchored by dosal and ventral mesogastrium. The space ouside this will be the peritoneal cavity.

Red ring-neural tube with neural crestBlue ring- notocordOrange- somites

Differentiation of associated organs at the level of the forming stomach occurs both dorsally (spleen) and ventrally (liver).

 

Large blue ring- dorsal aortaDark green ring- Liver

Continued growth of the GIT and the organs leads to organ movements and bending of tract.

Carnegie stage 13 Embryo Overview

Below is an overview of the sections starting at the level of pharynx compressed dorsoventrally, following the GIT through to the rectum. The most obvious feature is that of a continuous tube initially, attached by dorsoventral mesentry. Outside this tube and mesentry (at the levels below the lung buds) is the intraembryonic coelom that will form the peritoneal cavity. The hepatic diverticulum (liver bud) lies under the septum transversum is the earliest associated GIT organ that has differentiated, and now occupies a substantial region of the abdomen. Clicking on sections below will open the original images.

Stage14-git.jpg
Bifurcation of the pharynx into anterior respiratory and posterior oesophagous. The stomach forming beneath the lung buds and adjacent to the developing liver. Below the stomach the GIT has a large dorsal mesogastrium and finer ventral mesogastrium. Associated with the tract is the large portal blood vessel derived from the vitelline circulation. At the bottom curvature of the embryo the mesentry association with the GIT shows extensive vitelline vessels running out through the umbilicus. The hindgut can then be seen, ending at the common urogenital sinus, the cloaca.

Innervation

Myenteric plexus lying between the outer two layers of smooth muscle

Neural History

  • 1857 Meissner was the first to describe a nerve plexus in the submucosa of the bowel wall.
  • 1864 Auerbach described the myenteric plexus between the longitudinal and circular muscle layers.
  • 1981 LeDouarin describes neural crest contribution to both plexuses.

Myenteric Plexus

  • Peristalsis
  • Coordinated waves of descending inhibition followed by waves of descending excitation

+ Extrinsic parasympathetic cholinergic nerves (vagal and sacral) excite peristalsis and stimulate

- Sympathetic noradrenergic nerves inhibit the transit of gut contents


Submucosal Plexus

  • epithelial movements
  • secretion and absorption

Associated Organs

Liver, pancreas and spleen (stage 22 embryo).

The early tract develops as a simple tube, then a number of endodermal outgrowths from this tube at different levels and contribute to a range of additional organs and tissues. The gastrointestinal associated organs liver, gall bladder and pancreas. Development of these organs is described on separate pages.

There are also a number of additional non-gastrointestinal structures including the respiratory tract and development within the mesentery such as the spleen.


Links: Liver | Gall Bladder | PancreasLiver Histology | Pancreas Histology | Gall Bladder Histology

Gastrointestinal Tract Abnormalities

Only a brief description is given on this current page, for more details see Gastrointestinal Tract - Abnormalities.

Lumen Abnormalities

There are several types of abnormalities that impact upon the continuity of the gastrointestinal tract lumen.

  • Atresia - interuption of the lumen (esophageal atresia, duodenal atresia, extrahepatic biliary atresia, anorectal atresia)
  • Stenosis - narrowing of the lumen (duodenal stenosis, pyloric stenosis).
  • Duplication - incomplete recanalization resulting in parallel lumens, this is really a specialized form of stenosis.

Meckel's Diverticulum

This GIT abnormality is a very common and results from improper closure and absorption of the omphalomesenteric duct (vitelline duct) in development. This transient developmental duct connects the yolk to the primitive GIT.

Intestinal Malrotation

Intestinal malrotation.jpg


Links: Intestinal Malrotation

Intestinal Aganglionosis

(intestinal aganglionosis, Hirschsprung's disease, aganglionic colon, megacolon, congenital aganglionic megacolon, congenital megacolon) A condition caused by the lack of enteric nervous system (neural ganglia) in the intestinal tract responsible for gastric motility (peristalsis).

Gastroschisis

Gastroschisis (omphalocele, paraomphalocele, laparoschisis, abdominoschisis, abdominal hernia) is a congenital abdominal wall defect which results in herniation of fetal abdominal viscera (intestines and/or organs) into the amniotic cavity. Incidence of gastroschisis has been reported at 1.66/10,000, occuring more frequently in young mothers (less than 20 years old).

By definition, it is a body wall musculoskeletal defect, not a gastrointestinal tract defect, which in turn impacts upon GIT development.

Links: Gastroschisis | Gastrointestinal Tract - Abnormalities

Molecular

The endoderm of the developing gastrointestinal tract is a source for patterning signals for both within the tract and also for the surrounding organs and tissues.


  • Sox2 - expressed in the anterior part of the primitive gutCite error: Invalid <ref> tag;

invalid names, e.g. too many

  • Cdx2 - expressed in the posterior part of the primitive gutCite error: Invalid <ref> tag;

invalid names, e.g. too many

  • GDNF - regulate migration of enteric neural crest cellsCite error: Invalid <ref> tag;

invalid names, e.g. too many

  • endothelin - regulate migration of enteric neural crest cellsCite error: Invalid <ref> tag;

invalid names, e.g. too many

References

  1. ↑ Peter S Vestentoft, Peter Jelnes, Branden M Hopkinson, Ben Vainer, Kjeld Møllgård, Bjørn Quistorff, Hanne C Bisgaard Three-dimensional reconstructions of intrahepatic bile duct tubulogenesis in human liver. BMC Dev. Biol.: 2011, 11();56 PMID:21943389
  2. ↑ Petra Dames, Ramona Puff, Michaela Weise, Klaus G Parhofer, Burkhard Göke, Magdalena Götz, Jochen Graw, Jack Favor, Andreas Lechner Relative roles of the different Pax6 domains for pancreatic alpha cell development. BMC Dev. Biol.: 2010, 10();39 PMID:20377917

Online Textbooks

Historic Textbooks

Reviews

Alan J Burns, Rachael R Roberts, Joel C Bornstein, Heather M Young Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages. Semin. Pediatr. Surg.: 2009, 18(4);196-205 PMID:19782301

Sally F Burn, Robert E Hill Left-right asymmetry in gut development: what happens next? Bioessays: 2009, 31(10);1026-37 PMID:19708022

Valérie A McLin, Susan J Henning, Milan Jamrich The role of the visceral mesoderm in the development of the gastrointestinal tract. Gastroenterology: 2009, 136(7);2074-91 PMID:19303014

H M Young On the outside looking in: longitudinal muscle development in the gut. Neurogastroenterol. Motil.: 2008, 20(5);431-3 PMID:18416699

Deborah C Rubin Intestinal morphogenesis. Curr. Opin. Gastroenterol.: 2007, 23(2);111-4 PMID:17268237

Josef Neu Gastrointestinal development and meeting the nutritional needs of premature infants. Am. J. Clin. Nutr.: 2007, 85(2);629S-634S PMID:17284768

Richard B Anderson, Donald F Newgreen, Heather M Young Neural crest and the development of the enteric nervous system. Adv. Exp. Med. Biol.: 2006, 589();181-96 PMID:17076282

Robert H Costa, Vladimir V Kalinichenko, Ai-Xuan L Holterman, Xinhe Wang Transcription factors in liver development, differentiation, and regeneration. Hepatology: 2003, 38(6);1331-47 PMID:14647040

P de Santa Barbara, G R van den Brink, D J Roberts Development and differentiation of the intestinal epithelium. Cell. Mol. Life Sci.: 2003, 60(7);1322-32 PMID:12943221

L R Johnson Functional development of the stomach. Annu. Rev. Physiol.: 1985, 47();199-215 PMID:3922287


Articles

Bettina Wilm, Annemieke Ipenberg, Nicholas D Hastie, John B E Burch, David M Bader The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature. Development: 2005, 132(23);5317-28 PMID:16284122


Search PubMed

Search Mar 2007 "gastrointestinal tract development" 29,361 reference articles of which 3,494 were reviews.

Search April 2010 "Gastrointestinal Tract Development" - All (35980) Review (4707) Free Full Text (8086)

Search Pubmed: Gastrointestinal Tract Development

Additional Images

  • Gitbpm.jpg
  • Gray0982a.jpg
  • Gray0982b.jpg
  • Gray0977.jpg
  • Gray0986.jpg
  • Gray0986.jpg

  • Historic image showing midgut herniation

  • Gray0991.jpg
  • Stage14-git.jpg

  • Historic human embryo (17.8mm)

  • Historic human embryo (17.8mm)

  • Historic human embryo (17.8mm)


System Links: Introduction | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Immune | Integumentary | Musculoskeletal | Neural | Neural Crest | Placenta | Renal | Respiratory | Sensory | Birth


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Dr Mark Hill 2013, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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