title: 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.
  
  
  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.affiliation: Developmental Biology Program, Children's Hospital Los Angeles, 4650 Sunset Boulevard, Smith Research Tower 804, Mail Stop #100, Los Angeles, CA 90027, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Fairbanks
authors.forename: R C
authors.initials: RC
authors.lastname: Kanard
authors.forename: S P
authors.initials: SP
authors.lastname: De Langhe
authors.forename: F G
authors.initials: FG
authors.lastname: Sala
authors.forename: P M
authors.initials: PM
authors.lastname: Del Moral
authors.forename: D
authors.initials: D
authors.lastname: Warburton
authors.forename: K D
authors.initials: KD
authors.lastname: Anderson
authors.forename: S
authors.initials: S
authors.lastname: Bellusci
authors.forename: R C
authors.initials: RC
authors.lastname: Burns
mesh_terms: D000818:Animals; D002432:Cecum / Q000378:metabolism; D005314:Embryonic and Fetal Development; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007409:Intestinal Atresia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007413:Intestinal Mucosa; D051379:Mice; D018345:Mice, Knockout; D009130:Muscle, Smooth / Q000196:embryology / Q000473:pathology; D009154:Mutation; D019683:Penetrance; D010528:Peristalsis; D051497:Receptor, Fibroblast Growth Factor, Type 2; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C496464:Fgf10 protein, mouse; D051526:Fibroblast Growth Factor 10; D017468:Receptors, Fibroblast Growth Factor; D005346:Fibroblast Growth Factors; D051497:Receptor, Fibroblast Growth Factor, Type 2