A developmental mechanism of intestinal villus malformation

Abstract

Abstract Introduction: The intestinal villi are a unique morphological component critical to intestinal function, and their malformation can lead to malabsorption, chronic wasting syndromes, and failure to thrive. The Fibroblast growth factor 10 (Fgf10) plays a critical role in gastrointestinal development and maturation. Fibronectin is an extracellular protein that forms an important part of the extracellular matrix and the basement membrane. The goal of the current study is to evaluate the role of the Fgf10 signaling pathway in epithelial growth and development by evaluating structural proteins. Methods: Transgenic Fgf10−/− and wild type (Wt) mice were bred, and near-term embryos were harvested from timed pregnancy mothers. The duodenum and proximal jejunum were harvested, fixed, and sectioned. They were then analyzed histologically and by immunofluorescent markers for epithelial structural proteins. Photomicrographs were taken. Results: The villi in the Fgf10−/− mutant mice are markedly abnormal. They are fewer in number, the crypt-villus height is shortened, and they have a broader base. On staining, fibronectin can be seen to form the basement membrane of the intestinal wall and penetrates each villus. In the mutant the fibronectin appears to pool at the bases of the villi, and there is a decreased amount of fibronectin inside each villus. Conclusions: The significance of these data is the normal development of epithelial architecture is dependent on the Fgf10 signaling pathway. Malformed villi, as seen with Fgf10 loss of function, result from improper distribution of fibronectin.