Crosstalk between Wnt and Notch signaling in intestinal epithelial cell fate decision

Continuous renewal of the intestinal epithelium requires coordinated regulation to maintain the balance between proliferation and differentiation of the epithelial stem cells and immature progenitor cells. Canonical Wnt signaling has long been regarded as the signaling pathway playing a central role in this epithelial cell fate determination; however, recent studies have shown that Notch signaling is also indispensable for this process. Here, we review the current concepts of how the Wnt and Notch pathways control intestinal epithelial cell fate decisions, particularly focusing on their crosstalk at both tissue and cellular levels. As several features are shared between stem cell renewal and cancer cell renewal, comprehensive understanding of how the Wnt and Notch signaling pathways cooperate and integrate in the gut epithelium has significant implications for the development of novel therapeutic modalities for intestinal neoplasia.