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.
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: Denise Al Alam; Soula Danopoulos; Kathy Schall; Frederic G Sala; Dana Almohazey; G Esteban Fernandez; Senta Georgia; Mark R Frey; Henri R Ford; Tracy Grikscheit; Saverio Bellusci Journal: Am J Physiol Gastrointest Liver Physiol Date: 2015-02-26 Impact factor: 4.052
Authors: Denise Al Alam; Frederic G Sala; Sheryl Baptista; Rosanna Galzote; Soula Danopoulos; Caterina Tiozzo; Philip Gage; Tracy Grikscheit; David Warburton; Mark R Frey; Saverio Bellusci Journal: Dev Biol Date: 2012-07-20 Impact factor: 3.582
Authors: Anna Kowalkowski; Krzysztof M Zaremba; Andrew P Rogers; Olivia R Hoffman; Anne E Turco; Peter F Nichol Journal: Dev Dyn Date: 2020-03-10 Impact factor: 3.780
Authors: Elie El Agha; Denise Al Alam; Gianni Carraro; Breanne MacKenzie; Kerstin Goth; Stijn P De Langhe; Robert Voswinckel; Mohammad K Hajihosseini; Virender K Rehan; Saverio Bellusci Journal: PLoS One Date: 2012-06-13 Impact factor: 3.240
Authors: Allison L Speer; Denise Al Alam; Frederic G Sala; Henri R Ford; Saverio Bellusci; Tracy C Grikscheit Journal: PLoS One Date: 2012-11-01 Impact factor: 3.240