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

• DOI: 10.7554/elife.72836
• Publication Date: 2022-10-21T12:00:33Z
• Authors: Jerome Bohere; Buffy L Eldridge-...; Golnar Kolahgar
• Keywords: 0301 basic medicine; Integrins; QH301-705.5; Science; 1.1 Normal biological development and functioning; regenerative medicine; Regenerative Medicine; developmental biology; 03 medical and health sciences; stem cells; Animals; Homeostasis; 1 Underpinning research; Biology (General); mechanotransduction; 0303 health sciences; D. melanogaster; vinculin; Q; R; intestinal homeostasis; differentiation; Cadherins; Stem Cell Research; Stem Cells and Regenerative Medicine; Vinculin; Actins; stem cell; Enterocytes; Medicine; Drosophila; Stem Cell Research - Nonembryonic - Non-Human; Generic health relevance; Digestive Diseases; alpha Catenin; Research Article; Developmental Biology

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 α-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 (EB), the two cells initially remain connected by adherens junctions, where vinculin is required, only on the EB side, to maintain the EB in a quiescent state and inhibit further divisions of the stem cell. By manipulating cell tension, we show that vinculin recruitment to adherens junction regulates EB activation and numbers. Consequently, removing vinculin results in an enlarged gut with improved resistance to starvation. Thus, mechanical regulation at the contact between stem cells and their progeny is used to control tissue cell number.