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

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 signalling, a key regulatory pathway of intestinal stem cells, and the expression and cellular localisation of Snai1. Strong nuclear expression of Snai1 was detected in the crypt base columnar (CBC) stem cells in the adult small intestine while Snai1 was mostly found in the cytoplasm of differentiated enterocytes and enteroendocrine cells. The expression and cellular localisation of Snai1 in the intestinal epithelium appears to be regulated by the canonical Wnt signalling pathway as Snai1 expression was dramatically reduced following conditional deletion of beta-catenin. Conversely, significant nuclear Snai1 was detected in polyps derived from Apcmin mice and in intestinal villi following conditional mutation of Apc in AhCre; Apcf/f mice indicating that upregulation of the Wnt pathway in the intestinal epithelium induces both increased expression and nuclear localisation of Snai1.