Vinculin recruitment to α-catenin halts the differentiation and maturation of enterocyte progenitors to maintain homeostasis of the Drosophila intestine.

Abstract

Mechanisms communicating changes in tissue stiffness and size are particularly relevant in the intestine, because it is subject to constant mechanical stresses caused by peristalsis of its variable content. Using the Drosophila intestinal epithelium, we investigate the role of vinculin, one of the best characterised mechanoeffectors, which functions in both cadherin and integrin adhesion complexes. We discovered that vinculin regulates cell fate decisions, by preventing precocious activation and differentiation of intestinal progenitors into absorptive cells. It achieves this in concert with -catenin at sites of cadherin adhesion, rather than as part of integrin function. Following asymmetric division of the stem cell into a stem cell and an enteroblast, the two cells initially remain connected by adherens junctions, where vinculin is required, only on the enteroblast side, to maintain the enteroblast in a quiescent state and inhibit further divisions of the stem cell. Removing vinculin increases enteroblast differentiation and numbers, resulting in an enlarged gut with improved ability to recover after starvation. Thus, mechanical regulation at the contact between stem cells and their progeny is used to control tissue cell number.