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UNSW Embryology

Gastrointestinal Tract Development - Molecular

© Dr Mark Hill (2011)

Acknowledgements

Introduction

The gastrointestinal tract (GIT) extending from the pharyngeal membrane to the cloacal membrane arises from the endoderm of the trilaminar embryo (week 2, 3). This page gives a summary of some molecular development of the GIT.

Gastrulation, means the formation of gut, but has been used in a more looser sense to to describe the formation of the trilaminar embryo. The epiblast layer, consisting of totipotential cells, derives all 3 embryo layers: endoderm, mesoderm and ectoderm. The induction of endoderm appears to be patterned by FGF4 signals from adjacent ectoderm and mesoderm within the primitive streak (Wells & Melton, 2000).

The notochord lying in the midline of the mesoderm patterns many surrpounding tissues including the underlying endoderm of the primitive gastrointestinal tract.

Page Links: Introduction | Some Recent Findings | Cdx2 | Notochord | Wnt |

Some Recent Findings

Natasza A. Kurpios, Marta Ibañes, Nicole M. Davis, Wei Lui, Tamar Katz, James F. Martin, Juan Carlos Izpisúa Belmonte, and Clifford J. Tabin. The direction of gut looping is established by changes in the extracellular matrix and in cell:cell adhesion PNAS 2008 105: 8499-8506; published online on June 23, 2008

"The counterclockwise coiling of the intestines is initiated by a leftward tilt of the primitive gut tube, imparted by left–right asymmetries in the architecture of the dorsal mesentery. ...We find that the dorsal mesentery extracellular matrix is indeed left–right asymmetric and moreover that the adhesion molecule N-cadherin is expressed exclusively on the left side."

Lees C, Howie S, Sartor RB, Satsangi J. The hedgehog signalling pathway in the gastrointestinal tract: implications for development, homeostasis, and disease. Gastroenterology. 2005 Nov;129(5):1696-710.

"Through epithelial-mesenchymal interactions, hedgehog signalling ensures appropriate axial patterning of the embryonic gut. Congenital abnormalities, including malrotations, anorectal malformations, and tracheoesophageal fistula are associated with germ-line mutations/deletion of genes encoding hedgehog signalling components in man and present in genetically engineered animal models."

Cdx2

Homeobox gene

Mouse - Cdx2 expression E12 onward confined to the intestinal epithelium (from a region just rostral to the hepatic diverticulum to the distal colon). In the adult, high levels of expression persist in the proximal colon gradually falling off in the ileum and jejunum cranially and in the distal colon caudally.

(Text modified from: Beck F. Homeobox genes in gut development. Gut. 2002 Sep;51(3):450-4. Review.)

Serls AE, Doherty S, Parvatiyar P, Wells JM, Deutsch GH.

Fibroblast Growth Factor

Serls AE, Doherty S, Parvatiyar P, Wells JM, Deutsch GH. Different thresholds of fibroblast growth factors pattern the ventral foregut into liver and lung. Development. 2005 Jan;132(1):35-47.

"....Together, the findings suggest that a concentration threshold of FGFs emanating from the cardiac mesoderm are involved in patterning the foregut endoderm."

Notochord

Cleaver O, Krieg PA. Notochord patterning of the endoderm. Dev Biol. 2001 Jun 1;234(1):1-12.

"Endodermally derived organs of the gastrointestinal and respiratory system form at distinct anterioposterior and dorsoventral locations along the vertebrate body axis. This stereotyped program of organ formation depends on the correct patterning of the endodermal epithelium so that organ differentiation and morphogenesis occur at appropriate positions along the gut tube. Whereas some initial patterning of the endoderm is known to occur early, during germ-layer formation and gastrulation, later signaling events, originating from a number of adjacent tissue layers, are essential for the development of endodermal organs. Previous studies have shown that signals arising from the notochord are important for patterning of the ectodermally derived floor plate of the neural tube and the mesodermally derived somites. This review will discuss recent evidence indicating that signals arising from the notochord also play a role in regulating endoderm development."

Links:

Wnt

Theodosiou NA, Tabin CJ. Wnt signaling during development of the gastrointestinal tract. Dev Biol. 2003 Jul 15;259(2):258-71.

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