Wnt signaling regulates Snai1 expression and cellular localization in the mouse intestinal epithelial stem cell niche

Abstract

Snail genes are transcriptional repressors well known to play important roles in epithelial to mesenchymal transitions during both embryogenesis and cancer metastasis. Although they are generally regarded as markers of mesenchymal cells, Snail genes have also recently been implicated in regulating stem cell populations in both Drosophila and vertebrates. In this study we investigate Snai1, a member of the mouse Snail family, in the intestinal stem cell niche and examine the relationship between canonical Wnt signaling, a key regulatory pathway of intestinal stem cells, and expression and cellular localization of Snai1. Strong nuclear expression of Snai1 was detected in the crypt base columnar stem cells in the adult small intestine while Snai1 was mostly found in the cytoplasm of differentiated enterocytes and enteroendocrine cells. Expression and cellular localization of Snai1 in the intestinal epithelium appears to be regulated by the canonical Wnt signaling pathway as Snai1 expression was dramatically reduced after conditional deletion of β-catenin. Conversely, significant nuclear Snai1 was detected in polyps derived from Apc(min) mice and in intestinal villi after conditional mutation of Apc in AhCre, Apc(f/f) mice, indicating that upregulation of the Wnt pathway in the intestinal epithelium induces both increased expression and nuclear localization of Snai1.