Gastrointestinal Tract Development

Introduction

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)

Historic Embryology - Gastrointestinal Tract
1878 Alimentary Canal \| 1882 The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs \| 1884 Great omentum and transverse mesocolon \| 1902 Meckel's diverticulum \| 1902 The Organs of Digestion \| 1903 Submaxillary Gland \| 1906 Liver \| 1907 Development of the Digestive System \| 1907 Atlas \| 1907 23 Somite Embryo \| 1908 Liver \| 1908 Liver and Vascular \| 1910 Mucous membrane Oesophagus to Small Intestine \| 1910 Large intestine and Vermiform process \| 1911-13 Intestine and Peritoneum - Part 1 \| Part 2 \| Part 3 \| Part 5 \| Part 6 \| 1912 Digestive Tract \| 1912 Stomach \| 1914 Digestive Tract \| 1914 Intestines \| 1914 Rectum \| 1915 Pharynx \| 1915 Intestinal Rotation \| 1917 Entodermal Canal \| 1918 Anatomy \| 1921 Alimentary Tube \| 1932 Gall Bladder \| 1939 Alimentary Canal Looping \| 1940 Duodenum anomalies \| 2008 Liver \| 2016 GIT Notes \| Historic Disclaimer
Human Embryo: 1908 13-14 Somite Embryo \| 1921 Liver Suspensory Ligament \| 1926 22 Somite Embryo \| 1907 23 Somite Embryo \| 1937 25 Somite Embryo \| 1914 27 Somite Embryo \| 1914 Week 7 Embryo
Animal Development: 1913 Chicken \| 1951 Frog

Template:Historic GIT

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."

More recent papers
This table allows an automated computer search of the external PubMed database using the listed "Search term" text link. This search now requires a manual link as the original PubMed extension has been disabled. The displayed list of references do not reflect any editorial selection of material based on content or relevance. References also appear on this list based upon the date of the actual page viewing. References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability. More? References \| Discussion Page \| Journal Searches \| 2019 References \| 2020 References Search term: Gastrointestinal Tract Embryology <pubmed limit=5>Gastrointestinal Tract Embryology</pubmed>

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

UNSW Students
	You have access the following online Embryology textbooks through the UNSW Library.
	Moore, K.L. & Persuad, T.V.N. (2008). The Developing Human: clinically oriented embryology (8^th ed.). Philadelphia: Saunders. Chapter 11 - The Digestive System (chapter links only work with a UNSW connection).
	Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R. and Francis-West, P.H. (2009). Larsen’s Human Embryology (4^th ed.). New York; Edinburgh: Churchill Livingstone. Chapter 14 - Development of the Gastrointestinal Tract (chapter links only work with a UNSW connection).

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

‎‎Week 3 Mesoderm

Page | Play

‎‎Week 3

Page | Play

‎‎Amniotic Cavity

Page | Play

‎‎Endoderm

Page | Play

‎‎Stomach Rotation

Page | Play

‎‎Tract Growth

Page | Play

‎‎Greater Omentum

Page | Play

‎‎Lesser sac

Page | Play

‎‎Urogenital Septum

Page | Play

‎‎GIT Stage 13

Page | Play

‎‎GIT Stage 22

Page | Play

‎‎Sagittal GIT

Page | Play

‎‎GIT Motility

Page | Play

‎‎Gastroschisis

Page | Play

‎‎Omphalocele

Page | Play

Stage 13 (week 5)

Stage 22 (week 8)

Stage 23 (week 8)

GIT Abnormalities Ultrasound

3 GIT divisions

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.


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 | Pancreas Liver 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

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 gut^[3]
Cdx2 - expressed in the posterior part of the primitive gut^[3]
GDNF - regulate migration of enteric neural crest cells^[4]
endothelin - regulate migration of enteric neural crest cells^[4]

References

↑ <pubmed>21943389</pubmed>
↑ <pubmed>20377917</pubmed>
↑ ^3.0 ^3.1 <pubmed>22679103</pubmed>
↑ ^4.0 ^4.1 <pubmed>23486961</pubmed>

Online Textbooks

Developmental Biology (6th ed) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. The Digestive Tube and Its Derivatives | Endodermal development of a human embryo
The Gastrointestinal Circulation Peter R. Kvietys. San Rafael (CA): Morgan & Claypool Publishers; 2010. Table of Contents
Motor Function of the Pharynx, Esophagus, and its Sphincters. Mittal RK. San Rafael (CA): Morgan & Claypool Life Sciences; 2011. Table of Contents
Search NLM Online Textbooks "gastrointestinal tract" : Developmental Biology | Endocrinology | Molecular Biology of the Cell | The Cell- A molecular Approach

Historic Textbooks

The Elements of Embryology by Foster, M., Balfour, F. M., Sedgwick, A., & Heape, W. (1883) The Alimentary Canal and its Appendages
Text-Book of the Embryology of Man and Mammals by Dr Oscar Hertwig (1892) The Organs of the Inner Germ-Layer The Alimentary Tube with its Appended Organs
Atlas of the Development of Man Volume 2 by Julius Kollmann (1907) Gastrointestinal
Text-Book of Embryology by Bailey, F.R. and Miller, A.M. (1921) Alimentary tube and organs

Historic Disclaimer - information about historic embryology pages
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding. (More? Embryology History \| Historic Embryology Papers)