A genetic mechanism for cecal atresia: the role of the Fgf10 signaling pathway.

Abstract

BACKGROUND:

Intestinal atresia represents a significant surgically correctable cause of intestinal obstruction in neonates. Intestinal development proceeds as a tube-like structure with differentiation along its axis. As the intestine differentiates, the cecum develops at the transition from small to large intestine. Fgf10 is known to serve a key role in budding morphogenesis; however, little is known about its role in the development of this transitional structure. Here we evaluate the effect of Fgf10/Fgfr2b invalidation on the developing cecum.

MATERIALS AND METHODS:

Wild-type C57Bl/6, Fgf10(-/-), and Fgfr2b(-/-) embryos harvested from timed pregnant mothers were analyzed for cecal phenotype, Fgf10 expression, and differentiation of smooth muscle actin.

RESULTS:

Wt cecal development is first evident at E11.5. FGF10 is discreetly expressed in the area of the developing cecum at early stages of development. One hundred percent of Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with absence of epithelial and muscular layers. The development of neighboring anatomical structures such as the ileocecal valve is not affected by Fgf10/Fgfr2b invalidation.

CONCLUSIONS:

FGF10 expression is localized to the cecum early in the normal development of the cecum. Fgf10(-/-) and Fgfr2b(-/-) mutant embryos demonstrate cecal atresia with complete penetrance. Epithelial and muscular layers of the cecum are not present in the atretic cecum. The Fgf10(-/-) and Fgfr2b(-/-) mutants represent a genetically reproducible animal model of autosomal recessive intestinal atresia.

• Authors: T J Fairbanks, R C Kanard, S P De Langhe, F G Sala, P M Del Moral, D Warburton, K D Anderson, S Bellusci, R C Burns
• Journal: The Journal of surgical research (J Surg Res) Vol. 120 Issue 2 Pg. 201-9 (Aug 2004) ISSN: 0022-4804 [Print] United States
• PMID: 15234214 (Publication Type: Journal Article)

Chemical References

• Fgf10 protein, mouse
• Fibroblast Growth Factor 10
• Receptors, Fibroblast Growth Factor
• Fibroblast Growth Factors
• Receptor, Fibroblast Growth Factor, Type 2

Topics

• Animals
• Cecum (metabolism)
• Embryonic and Fetal Development
• Fibroblast Growth Factor 10
• Fibroblast Growth Factors (deficiency, genetics, metabolism)
• Intestinal Atresia (etiology, metabolism, pathology, physiopathology)
• Intestinal Mucosa
• Mice
• Mice, Knockout
• Muscle, Smooth (embryology, pathology)
• Mutation
• Penetrance
• Peristalsis
• Receptor, Fibroblast Growth Factor, Type 2
• Receptors, Fibroblast Growth Factor (deficiency, genetics, metabolism)
• Signal Transduction