Gastrointestinal Tract - Intestine Development
|Embryology - 26 Feb 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Adult Small Intestine
- 4 Embryonic Development
- 5 Rotation
- 6 Fetal Intestine Length
- 7 Small Intestine Length
- 8 Appendix
- 9 Hindgut
- 10 Intestinal Motility
- 11 Abnormalities
- 12 Molecular Factors
- 13 References
- 14 Additional Images
- 15 External Links
- 16 Glossary Links
The part of the gastrointestinal tract (GIT) lying between the stomach and anus, is described as the intestines or bowel. This region is further divided anatomically and functionally into the small intestine or bowel (duodenum, jejunum and ileum) and large intestine or bowel (cecum and colon). Initially development concerns the midgut region, connected to the yolk sac, and the hindgut region, ending at the cloacal membrane. This is followed by two mechanical processes of elongation and rotation. Elongation, growth in length, leaves the midgut "herniated" at the umbilicus and external to the abdomen. Rotation, around a mesentery axis, establishes the anatomical position of the large intestine within the peritoneal space.
Migration of neural crest cells into the wall establishes the enteric nervous system, which has a role in peristalsis and secretion. Prenatally, secretions also accumulate in this region and are the first postnatal bowel movement, the meconium.
The small intestine grows in length rapidly in the last trimester, at birth it is about half the eventual adult length (More? Small Intestine Length). Like most of the gut, this region is not "functional" until after birth, when development continues by populating the large intestine with commensal bacteria and the establishment of the immune structure in the wall.
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.
Dongming Wang, Jingnian Pan, Guoxin Song, Ni Gao, Yi Zheng, Qiangye Zhang, Aiwu Li Abundance and Significance of Neuroligin-1 and Neurexin II in the Enteric Nervous System of Embryonic Rats. Biomed Res Int: 2017, 2017;1209360 PubMed 28194405
Roeland Buckinx, Katrien Alpaerts, Isabel Pintelon, Nathalie Cools, Luc Van Nassauw, Dirk Adriaensen, Jean-Pierre Timmermans In situ proximity of CX3CR1-positive mononuclear phagocytes and VIP-ergic nerve fibers suggests VIP-ergic immunomodulation in the mouse ileum. Cell Tissue Res.: 2017; PubMed 28190088
M Inan, E Bakar, A Cerkezkayabekir, F Sanal, E Ulucam, C Subaşı, E Karaöz Mesenchymal stem cells increase antioxidant capacity in intestinal ischemia/reperfusion damage. J. Pediatr. Surg.: 2017; PubMed 28118930
Oscar F Chacon-Camacho, Martin Zenker, Denny Schanze, Jasbeth Ledesma-Gil, Juan C Zenteno Novel FREM1 mutations in a patient with MOTA syndrome: Clinical findings, mutation update and review of FREM1-related disorders literature. Eur J Med Genet: 2017, 60(3);190-194 PubMed 28111185
Nandor Nagy, Allan M Goldstein Enteric nervous system development: A crest cell's journey from neural tube to colon. Semin. Cell Dev. Biol.: 2017; PubMed 28087321
Adult Small Intestine
|Duodenum||Jejunum and ileum|
- Duodenum (adult 25 cm length)
- Jejunum (adult 1.4 m length)
- Ileum (adult 3.5 m length)
The adult ileum contains specialised aggregated lymphoid nodules known as Peyer's patches.
|Adult jejunum histology||Adult ileum Peyer's patches|
Large intestine or bowel
- Cecum (caecum)
- Vermiform appendix ("appendix", adult 2 to 20 cm length)
- Ascending colon (adult 25 cm length)
- Transverse colon
- Descending colon
- Sigmoid colon
- absorption of nutrients and minerals found in food
- Duodenum -principal site for iron absorption
- connects the ileum with the ascending colon
- separated by the ileocecal valve (ICV, Bauhin's valve)
- connected to the vermiform appendix ("appendix")
- absorbs fluid, water and salts, from solid wastes
- site of commensal bacteria (flora) fermentation of unabsorbed material
Human embryo small intestine secondary loops (week 7 to 8).
Late embryonic small intestine commencing at the duodenum, continuing as ventrally herniated and returning to join the colon.
Small intestine tertiary loops week 8.
A recent 3 dimensional study has suggested a modified “en-bloc rotation” of the small intestine, compared the the earlier simplified description of 270 degree rotation (below).
Human intestine “en-bloc rotation” model.
- "If one insists on using the term rotation for this movement, it would be largely around a craniocaudal axis (in the transverse plane) rather than a dorsoventral axis (frontal plane). In view of the brief time window and orientation of the apparent rotational axis, we conclude that the distal ileum and cecum “slide” rather than “rotate” as from the umbilical orifice to the lower-right abdominal cavity."
Normal intestinal rotation
Fetal Intestine Length
|Fetal small Intestine length growth||Fetal Large Intestine length growth|
Small Intestine Length
Small intestine growth in length is initially linear (first half pregnancy to 32 cm CRL), followed by rapid growth in the last 15 weeks doubling the overall length. Growth continues postnatally but after 1 year slows again to a linear increase to adulthood.
|Age (weeks gestational age)||Average Length (cm)|
|1 year postnatal||380|
Table data based upon 8 published reports of necropsy measurement of 1010 guts.
The appendix (vermiform appendix, vermix) is a finger-like diverticulum located anatomically at the cecum, the junction between the small and large intestines (colon). The length (2.5-13 cm) is longer in both infants and children and also has more abundant lymphatic tissue in early life. The wall structure is similar to the small intestine (though with no villi), nor plicae circularis. Its immune function is associated with the many lymph nodules surrounding the lumen that extend from the mucosa into the submucosa. It has also been suggested as a repository for beneficial intestinal microflora. See also the review comparing the appendix in different species.
There appears to be a developmental anatomical differences in the fetal position of the appendix in males and females. In the fetus, lymphocyte aggregates first appear in this region during the second trimester, week 15 (GA week 17).
Historically, Berengario da Carpi (1460-c.1530) in Commentaria cum amplissimis additionibus super Anatomia Mundini (1521) was the first to describe the human appendix.
Anatomically the distal third of the transverse colon and the splenic flexure, the descending colon, sigmoid colon and rectum. The developmental timing of the anus and rectum formation in human embryos of the Carnegie Collection has been previously carried out (1974). A more recent study has also been made of the Kyoto Collection embryos.
There has been some recent controversy over the "anal membrane" formation.
A recent study hindgut and anorectum development in human embryos shows that Wnt5a is active in this region prior to anus formation, when it is down-regulated.
The enteric nervous system neural crest-derived neurons interacts with the circular and longitudinal smooth muscle layers and the interstitial cells of Cajal to generate motility. The developmental timing data shown below is from a recent review.
week 5 - migrating neural crest cells reach the midgut
week 7 - neural crest cells have colonized the entire gut
- colonization occurs in a rostro-caudal sequence
Myenteric plexus (Auerbach's plexus, named after Leopold Auerbach (1828–1897) a German anatomist and neuropathologist.)
- is first formed plexus
- lies between the outer longitudinal and inner circular layers of muscularis externa
- provides motor innervation to both layers
- secretomotor innervation to the mucosa
- has both parasympathetic and sympathetic input
Submucosal Plexus (Meissner's plexus, named after Georg Meissner (1829–1905) a German anatomist and physiologist.)
- forms 2-3 days after the myenteric plexus
- formed by cells migrating from the myenteric plexus
- innervates smooth muscle of the muscularis mucosae
- has only parasympathetic fibers
week 8 - esophagus circular muscle
week 11 - hindgut circular muscle
week 14 - hindgut concentric muscularis mucosae, circular muscle, and longitudinal muscle
Interstitial Cells of Cajal
Interstitial cells of Cajal (ICC) are electrical pacemaker cells within the gastrointestinal tract smooth muscle. They create the basal (slow waves) rhythm required for contraction and peristalsis. They are mesodermal in origin.
weeks 7-9 - cells initially appear
week 11 - distinct clusters
week 12-14 - clustered around myenteric ganglia along the entire gut
- Links: Neural Crest Development
- Abnormality Links: Gastrointestinal Tract - Abnormalities | Intestine Development | Gastrointestinal Tract
- Lumen Abnormalities: Image - Duplication sites | Pyloric atresia | Jejunal atresia
- Rotation: Image - Midgut volvulus | Image - Intestinal malrotation | Image - Cecal volvulus | Image - Sigmoid volvulus | Ladd's band
- Meckel's Diverticulum: Meckel's Image 1 | Meckel's Image 2 | Meckel's Image 3 |
- Intestinal Aganglionosis: Image - Ostomy | Image - Stoma | Surgery 1 | Surgery 2 | Surgery 3
Appendix duplication is an extremely rare congenital anomaly (0.004% to 0.009% of appendectomy specimens) first classified according to their anatomic location by Cave in 1936 and a later modified by Wallbridge in 1963, subsequently two more types of appendix abnormalities have been identified.
Modified Cave-Wallbridge Classification (table from)
| Classification of types
of appendix duplication
|A||Single cecum with various degrees of incomplete duplication|
|B1 (bird type)||Two appendixes symmetrically placed on either side of the ileocecal valve|
|B2 (tenia coli type)|| ne appendix arises from the cecum at the usual site, and the second
appendix branches from the cecum along the lines of the tenia at various distances from the first
|B3|| One appendix arises from the usual site, and the second appendix arises from
the hepatic flexura
|B4|| One appendix arises from the usual site, and the second appendix arises from
the splenic flexura
|C||Double cecum, each with an appendix|
|Horseshoe appendix||One appendix has two openings into a common cecum|
|Triple appendix||One appendix arises from the cecum at the usual site, and two additional appendixes arise from the colon|
Short Bowel Syndrome
Short bowel syndrome (SBS) results typically due to developmental abnormalities, extensive intestinal resection during the neonatal period, or necrotising enterolitis.
- reduces gut function for digestion and absorption of nutrients (intestinal failure).
- Cdx (Caudal-type homeobox) group of ParaHox genes (mouse Cdx1, Cdx2 and Cdx4)
- Kun Xu, Xinyu Wu, Ellen Shapiro, Honging Huang, Lixia Zhang, Duane Hickling, Yan Deng, Peng Lee, Juan Li, Herbert Lepor, Irina Grishina Bmp7 functions via a polarity mechanism to promote cloacal septation. PLoS ONE: 2012, 7(1);e29372 PubMed 22253716
- 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
- James M Wells, Jason R Spence How to make an intestine. Development: 2014, 141(4);752-60 PubMed 24496613 | Development
- Michael J Geske, Xiuqin Zhang, Khushbu K Patel, David M Ornitz, Thaddeus S Stappenbeck Fgf9 signaling regulates small intestinal elongation and mesenchymal development. Development: 2008, 135(17);2959-68 PubMed 18653563
- Jelly Hm Soffers, Jill Pjm Hikspoors, Hayelom K Mekonen, S Eleonore Koehler, Wouter H Lamers The growth pattern of the human intestine and its mesentery. BMC Dev. Biol.: 2015, 15(1);31 PubMed 26297675
- Vicki Martin, Charles Shaw-Smith Review of genetic factors in intestinal malrotation. Pediatr. Surg. Int.: 2010, 26(8);769-81 PubMed 20549505 | PMC2908440
- J FitzSimmons, A Chinn, T H Shepard Normal length of the human fetal gastrointestinal tract. Pediatr Pathol: 1988, 8(6);633-41 PubMed 3244599
- John G Archie, Julianne S Collins, Robert Roger Lebel Quantitative standards for fetal and neonatal autopsy. Am. J. Clin. Pathol.: 2006, 126(2);256-65 PubMed 16891202
- L T Weaver, S Austin, T J Cole Small intestinal length: a factor essential for gut adaptation. Gut: 1991, 32(11);1321-3 PubMed 1752463 | PMC1379160 | Gut.
- R E Fisher The primate appendix: a reassessment. Anat. Rec.: 2000, 261(6);228-36 PubMed 11135184
- M A Malas, A Gökçimen, O Sulak Growing of caecum and vermiform appendix during the fetal period. Fetal. Diagn. Ther.: 2001, 16(3);173-7 PubMed 11316934
- M Ali Malas, O Sulak, A Gökçimen, A Sari Development of the vermiform appendix during the fetal period. Surg Radiol Anat: 2004, 26(3);202-7 PubMed 15173960
- de Vries PA. and Friedland GW. The staged sequential development of the anus and rectum in human embryos and fetuses. (1974) J. Pediatr. Sure., 9(5): 755-69 PMID 4424274
- Ryozo Hashimoto Development of the human tail bud and splanchnic mesenchyme. Congenit Anom (Kyoto): 2013, 53(1);27-33 PubMed 23480355
- Fei Fei Li, Tao Zhang, Yu Zuo Bai, Zheng Wei Yuan, Wei Lin Wang Spatiotemporal expression of Wnt5a during the development of the hindgut and anorectum in human embryos. Int J Colorectal Dis: 2011, 26(8);983-8 PubMed 21431850
- 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
- A J Cave Appendix Vermiformis Duplex. J. Anat.: 1936, 70(Pt 2);283-92 PubMed 17104589
- P H WALLBRIDGE Double appendix. Br J Surg: 1962, 50;346-7 PubMed 13998581
- T W Mesko, R Lugo, T Breitholtz Horseshoe anomaly of the appendix: a previously undescribed entity. Surgery: 1989, 106(3);563-6 PubMed 2772830
- L F Tinckler Triple appendix vermiformis--a unique case. Br J Surg: 1968, 55(1);79-81 PubMed 5635427
- Emel Canbay, Emel Akman Appendix perforation in appendix duplication in a man: a case report. J Med Case Rep: 2011, 5;162 PubMed 21513538 | J Medical Case Reports | PDF
- G Davì, A Pinto, M G Palumbo, V Gallo, A Mazza, A Strano Dipyridamole and aspirin in arteriosclerosis obliterans of the lower limbs. Adv. Prostaglandin Thromboxane Leukot. Res.: 1985, 13;271-5 PubMed 3159212
- Felix Beck, Emma J Stringer The role of Cdx genes in the gut and in axial development. Biochem. Soc. Trans.: 2010, 38(2);353-7 PubMed 20298182
James M Wells, Jason R Spence How to make an intestine. Development: 2014, 141(4);752-60 PubMed 24496613
Taeko K Noah, Bridgitte Donahue, Noah F Shroyer Intestinal development and differentiation. Exp. Cell Res.: 2011, 317(19);2702-10 PubMed 21978911
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
Jelly Hm Soffers, Jill Pjm Hikspoors, Hayelom K Mekonen, S Eleonore Koehler, Wouter H Lamers The growth pattern of the human intestine and its mesentery. BMC Dev. Biol.: 2015, 15(1);31 PubMed 26297675
Yui Ueda, Shigehito Yamada, Chigako Uwabe, Katsumi Kose, Tetsuya Takakuwa Intestinal rotation and physiological umbilical herniation during the embryonic period. Anat Rec (Hoboken): 2015; PubMed 26599074
Tae-Hee Kim, Byeong-Moo Kim, Junhao Mao, Sheldon Rowan, Ramesh A Shivdasani Endodermal Hedgehog signals modulate Notch pathway activity in the developing digestive tract mesenchyme. Development: 2011, 138(15);3225-33 PubMed 21750033
Won Kyu Kim, Hyun Kim, Dae Ho Ahn, Myoung Hee Kim, Hyoung Woo Park Timetable for intestinal rotation in staged human embryos and fetuses. Birth Defects Res. Part A Clin. Mol. Teratol.: 2003, 67(11);941-5 PubMed 14745932
Search Bookshelf Intestine Development
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Frazer JE. and Robbins RH. On the factors concerned in causing rotation of the intestine in man. (1915) J Anat Physiol. 50(1): 75-110. PMID 17233053
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