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Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway

Journal of Pediatric Surgery
Publication Date
DOI: 10.1016/j.jpedsurg.2004.10.023
  • Medicine


Abstract Background/Purpose Colonic atresia occurs in 1:20,000 live births, offering a neonatal surgical challenge. Prenatal expression of fibroblast growth factor 10 ( Fgf10), acting through fibroblast growth factor receptor 2b ( Fgfr2b), is critical to the normal development of the colon. Invalidation of the Fgf10 pathway results in colonic atresia, inherited in an autosomal recessive pattern. Classically, disturbance of the mesenteric vasculature has been thought to cause many forms of intestinal atresia. The purpose of this study was to evaluate the role of vascular occlusion in the pathogenesis of colonic atresia. Methods Wild type (Wt), Fgf10 − /− , and Fgfr2b − /− mutant mouse embryos were harvested from timed pregnant mothers. Immediately following harvest, filtered India ink was infused via intracardiac microinjection. The gastrointestinal tract was dissected, and photomicrographs of the mesenteric arterial anatomy were taken at key developmental time points. Results Photomicrographs after India ink microinjections demonstrate normal, patent mesenteric cascades to the atretic colon at the time points corresponding to the failure of colonic development in the Fgf10 − /− and Fgfr2b − /− mutants. The mesenteric arterial anatomy of the colon demonstrates no difference between the Wt and mutant colonic atresia. Conclusions The absence of embryonic expression of Fgf10 or its receptor Fgfr2b results in colonic atresia in mice. India ink microinjection is a direct measure of mesenteric arterial patency. Colonic atresia in the Fgf10 − /− and Fgfr2b − /− mutants occurs despite normal mesenteric vascular development. Thus the atresia is not the result of a mesenteric vascular occlusion. The patent colonic mesentery of the Fgf10 − /− and Fgfr2b − /− mutants challenges an accepted pathogenesis of intestinal atresia. Although colonic atresia can occur as a result of vascular occlusion, new evidence exists to suggest that a genetic mechanism may play a role in the pathogenesis of this disease.

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