Chapter 7 - WNT Signaling in the Intestine: Development, Homeostasis, Disease

Abstract

The intestine is a complex organ that has evolved to maximize the luminal surface area for the purpose of absorbing nutrients. The epithelial lining of the intestine must maintain itself in the face of a constant challenges from environmental factors such as microbes and food. Maintaining this epithelial lining, highly organized structure and cellular diversity is a highly proliferative population of intestinal stem cells. Intestinal stem cells are found in the crypt of Lieberkühn, which is the functional unit forming the stem cell niche. Aberrant regulation or mutations within the stem cells can lead to gastrointestinal pathologies. The niche within the crypt is complex, made up of cell-cell interactions, extracellular matrix and signaling pathways; chief among these is the WNT signaling pathway. The intestine has become a well-studied paradigmatic model system for understanding WNT signaling and its role in stem cell dynamics. The spatial restriction of WNT ligands by other pathway modulators, such as RSPO proteins, functions to balance the long term maintenance of intestinal stem cells while encouraging the rapid production of new progeny required for continual renewal of the epithelium in order to conduct its absorptive and protective roles. This chapter will specifically focus on the role of WNT signaling in the maintenance of intestinal stem cells, and will discuss the outcomes when this system is perturbed.