Gastrointestinal Tract Development
|Embryology - 26 Sep 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Textbooks
- 4 Objectives
- 5 Germ Layer Contributions
- 6 Gastrointestinal Tract Movies
- 7 3 GIT divisions
- 8 Development Overview
- 9 Carnegie stage 13 Embryo Overview
- 10 Innervation
- 11 Associated Organs
- 12 Gastrointestinal Tract Abnormalities
- 13 Molecular
- 14 References
- 15 Additional Images
- 16 Terms
- 17 Glossary Links
The gastrointestinal tract (GIT) arises initially during the process of gastrulation from the endoderm of the trilaminar embryo (week 3) and extends from the buccopharyngeal membrane to the cloacal membrane. The tract and associated organs later have contributions from all the germ cell layers.
During the 4th week three distinct regions (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.
The oral cavity (mouth) is formed following breakdown of the buccopharyngeal membrane (oropharyngeal or oral membrane) and contributed to mainly by the pharynx lying within the pharyngeal arches (More? Head Development). Loss of buccopharyngeal membrane opens the tract to amniotic fluid through the remainder of development, and during the fetal period is actively swallowed.
From the oral cavity the next portion of the foregut is initially the pharynx, a single gastrointestinal (oesophagus) and respiratory (trachea) common tube, that lies behind the heart. Note that the respiratory tract will form from a ventral bud arising at this level (More? Respiratory).
This current page provides an introductory overview, use the links below for descriptions of specific components and regions as well as developmental abnormalities.
Note that in historic texts the term entoderm is used to describe endoderm and other terminology may also differ from current descriptions.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
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.
Takeru Matsuda, Yasuo Sumi, Kimihiro Yamashita, Hiroshi Hasegawa, Masashi Yamamoto, Yoshiko Matsuda, Shingo Kanaji, Taro Oshikiri, Tetsu Nakamura, Satoshi Suzuki, Yoshihiro Kakeji Anatomy of the Transverse Mesocolon Based on Embryology for Laparoscopic Complete Mesocolic Excision of Right-Sided Colon Cancer. Ann. Surg. Oncol.: 2017; PubMed 28871557
Mehmet Kalayci, Mehmet Ali Kocdor, Tuncay Kuloglu, İbrahim Sahin, Mehmet Sarac, Aziz Aksoy, Meltem Yardim, Semih Dalkilic, Onur Gursu, Suna Aydin, Ramazan Fazil Akkoc, Meltem Cokugras, Gokhan Artas, İbrahim Hanifi Ozercan, Kader Ugur, Suleyman Aydin Comparison of the therapeutic effects of sildenafil citrate, heparin and neuropeptides in a rat model of acetic acid-induced gastric ulcer. Life Sci.: 2017; PubMed 28807720
Hongjun Shi, Annabelle Enriquez, Melissa Rapadas, Ella M M A Martin, Roni Wang, Julie Moreau, Chai K Lim, Justin O Szot, Eddie Ip, James N Hughes, Kotaro Sugimoto, David T Humphreys, Aideen M McInerney-Leo, Paul J Leo, Ghassan J Maghzal, Jake Halliday, Janine Smith, Alison Colley, Paul R Mark, Felicity Collins, David O Sillence, David S Winlaw, Joshua W K Ho, Gilles J Guillemin, Matthew A Brown, Kazu Kikuchi, Paul Q Thomas, Roland Stocker, Eleni Giannoulatou, Gavin Chapman, Emma L Duncan, Duncan B Sparrow, Sally L Dunwoodie NAD Deficiency, Congenital Malformations, and Niacin Supplementation. N. Engl. J. Med.: 2017, 377(6);544-552 PubMed 28792876
Sanja Z Despotović, Novica M Milićević, Dragoslav P Milošević, Nebojša Despotović, Predrag Erceg, Petar Svorcan, Udo Schumacher, Sebastian Ullrich, Gordana Mihajlović, Dragan Kalem, Srđan Marković, Ivana M Lalić, Aleksandar J Krmpot, Mihailo D Rabasović, Dejan V Pantelić, Svetlana Z Jovanić, Thomas Rösch, Živana Milićević Remodeling of extracellular matrix of the lamina propria in the uninvolved human rectal mucosa 10 and 20 cm away from the malignant tumor. Tumour Biol.: 2017, 39(7);1010428317711654 PubMed 28718368
Joshua T Byers, Dingle Foote, Patrick Choi, Samuel W French Foregut duplication cyst with pseudostratified columnar ciliated epithelium: A case report and review of the literature. Exp. Mol. Pathol.: 2017, 103(1);84-86 PubMed 28716574
- 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
|You have access the following online Embryology resources and textbooks through the UNSW Library.|
| Hill, M.A. (2017). UNSW Embryology (17th ed.) Retrieved September 26, 2017, from https://embryology.med.unsw.edu.au
| Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders. (links only function with UNSW connection)
Chapter 11 Alimentary System
| Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.(links only function with UNSW connection)
Chapter 14 Development of the Gastrointestinal Tract
- 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
|Gastrointestinal Tract Movies|
|Stage 13 (week 5)||Stage 22 (week 8)||Stage 23 (week 8)||GIT Abnormalities Ultrasound|
3 GIT 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.
- Oral cavity
- Pharynx (esophagus, trachea)
- Respiratory tract
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.
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
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.|
The gastrointestinal tract has both intrinsic and extrinsic innervation. (see the recent review)
- The intrinsic innervation, the enteric plexus, is derived from neural crest cells migrating into and along the wall of the gastrointestinal tract.
- mainly vagal region neural crest - generating both neurons and glia.
- some sacral neural crest - in chicken.
- The extrinsic innervation occurs by efferent and afferent nerves, from the vagus and sympathetic chain and pelvic nerves.
- Vagus - sensory and motor fibers project from oesophagus to small intestine.
- Sympathetic and parasympathetic - lower oesophagus to large intestine.
- Pelvic nerves - large intestine, rectum.
- 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.
- 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
- epithelial movements
- secretion and absorption
- Links: Neural Crest Development
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.
Gastrointestinal Tract Abnormalities
Only a brief description is given on this current page, for more details see Gastrointestinal Tract - 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.
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.
- Links: Intestinal Malrotation
(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 (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.
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
- Cdx2 - expressed in the posterior part of the primitive gut
- GDNF - regulate migration of enteric neural crest cells
- endothelin - regulate migration of enteric neural crest cells
- Adam Davis, Nirav M Amin, Caroline Johnson, Kristen Bagley, H Troy Ghashghaei, Nanette Nascone-Yoder Stomach curvature is generated by left-right asymmetric gut morphogenesis. Development: 2017, 144(8);1477-1483 PubMed 28242610
- Saki Ueno, Shigehito Yamada, Chigako Uwabe, Jörg Männer, Naoto Shiraki, Tetsuya Takakuwa The Digestive Tract and Derived Primordia Differentiate by Following a Precise Timeline in Human Embryos Between Carnegie Stages 11 and 13. Anat Rec (Hoboken): 2016, 299(4);439-449 PubMed 26995337
- 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 PubMed 21943389
- 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 PubMed 20377917
- Toshihiro Uesaka, Heather M Young, Vassilis Pachnis, Hideki Enomoto Development of the intrinsic and extrinsic innervation of the gut. Dev. Biol.: 2016; PubMed 27112528
- A J Burns, D Champeval, N M Le Douarin Sacral neural crest cells colonise aganglionic hindgut in vivo but fail to compensate for lack of enteric ganglia. Dev. Biol.: 2000, 219(1);30-43 PubMed 10677253
- Lalini Raghoebir, Elvira R M Bakker, Jason C Mills, Sigrid Swagemakers, Marjon Buscop-van Kempen, Anne Boerema-de Munck, Siska Driegen, Dies Meijer, Frank Grosveld, Dick Tibboel, Ron Smits, Robbert J Rottier SOX2 redirects the developmental fate of the intestinal epithelium toward a premature gastric phenotype. J Mol Cell Biol: 2012, 4(6);377-85 PubMed 22679103
- Akihiro Goto, Kenta Sumiyama, Yuji Kamioka, Eiji Nakasyo, Keisuke Ito, Mitsuhiro Iwasaki, Hideki Enomoto, Michiyuki Matsuda GDNF and endothelin 3 regulate migration of enteric neural crest-derived cells via protein kinase A and Rac1. J. Neurosci.: 2013, 33(11);4901-12 PubMed 23486961
- 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
- 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|
|Embryology History | Historic Embryology Papers)|
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 PubMed 19782301
Sally F Burn, Robert E Hill Left-right asymmetry in gut development: what happens next? Bioessays: 2009, 31(10);1026-37 PubMed 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 PubMed 19303014
H M Young On the outside looking in: longitudinal muscle development in the gut. Neurogastroenterol. Motil.: 2008, 20(5);431-3 PubMed 18416699
Deborah C Rubin Intestinal morphogenesis. Curr. Opin. Gastroenterol.: 2007, 23(2);111-4 PubMed 17268237
Josef Neu Gastrointestinal development and meeting the nutritional needs of premature infants. Am. J. Clin. Nutr.: 2007, 85(2);629S-634S PubMed 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 PubMed 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 PubMed 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 PubMed 12943221
L R Johnson Functional development of the stomach. Annu. Rev. Physiol.: 1985, 47;199-215 PubMed 3922287
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 PubMed 16284122
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)
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Cite this page: Hill, M.A. 2017 Embryology Gastrointestinal Tract Development. Retrieved September 26, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Gastrointestinal_Tract_Development
- © Dr Mark Hill 2017, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G