The role of vasculogenesis in the pathogenesis of intestinal atresia

Abstract

Abstract Introduction: Invalidation of the Fibroblast growth factor 10 (Fgf10) pathway results in colonic atresia. Fetal liver kinase (Flk-1), a receptor for vascular endothelial growth factor, is critical for vasculogenesis. The goal of the current study is to evaluate the role of vasculogenesis (via Flk-1 expression), as a pathogenic factor in the colonic atresia caused by the deletion of Fgf10. Methods: Fgf10−/−, Fgf10nlacZ/+ & Flk-1nlacZ/+ mutant mouse strains were crossed, creating mutant embryos with colonic atresia expressing a lacZ reporter gene under to the control of the promoter for Flk-1, Fgf10 or both. Photographs were taken of the colon at developmental stages E10.5 - E18.5 after treatment with X-Gal. Results: Fgf10 is expressed in the colon and Flk-1 is expressed in the mesenteric vasculature and end organ capillaries. Fgf10−/− Flk-1nlacZ/+ mutant embryos demonstrate normal mesenteric vasculature. The capillaries of mutant colonic tissue express Flk-1 at time points relevant to the pathogenesis of colonic atresia. This pattern is similar to that of the control wild type colon. Conclusions: This data demonstrates the expression of Fgf10 in the colon, and Flk-1 in the developing vasculature of mutant and control intestine. Flk-1 staining in the end organ capillary network of mutant atretic colonic tissue indicates there is no direct down regulation of the Flk-1 pathway in the Fgf10−/− mutant. Contrary to accepted theories of intestinal atresia, colonic atresia in the Fgf10−/− mutant is not due to a failure of vascular development.