Epithelial-mesenchymal interactions that govern the development of the colon from the primitive gastrointestinal tract are still unclear. In this study, we determine the temporal-spatial expression pattern of Fibroblast growth factor 10 (Fgf10), a key developmental gene, in the colon at different developmental stages. We found that Fgf10 is expressed in the mesenchyme of the distal colon, while its main receptor Fgfr2-IIIb is expressed throughout the entire intestinal epithelium. We demonstrate that Fgf10 inactivation leads to decreased proliferation and increased cell apoptosis in the colonic epithelium at E10.5, therefore resulting in distal colonic atresia. Using newly described Fgf10 hypomorphic mice, we show that high levels of FGF10 are dispensable for the differentiation of the colonic epithelium. Our work unravels for the first time the pivotal role of FGF10 in the survival and proliferation of the colonic epithelium, biological activities which are essential for colonic crypt formation.

No abstract

No abstract

No abstract

We have previously reported that fibroblast growth factor 10 (FGF10) is crucial for the survival and proliferation of progenitor cells during embryonic gastrointestinal development. We sought to characterize the potential role of FGF10 signaling in the adaptive response following small bowel resection. Adult wild-type and Fgf10 LacZ mice underwent 50% small bowel resection (SBR) or sham operation. Tissues were harvested 24 or 48 hr after surgery for histology, immunohistochemistry, and in situ hybridization. After SBR, Fgf10 expression was demonstrated in the epithelium at the base of the crypts. Moreover, there was a statistically significant increase in proliferating cells and goblet cells after SBR. In vitro studies using rat intestinal epithelial crypt (IEC-6) cells exposed to medium with or without recombinant FGF10 showed increased proliferation and phosphorylation of Raf and AKT with the addition of FGF10. Our results suggest that FGF10 may play a therapeutic role in diseases involving intestinal failure. Developmental Dynamics 238:294 -301, 2009.