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

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Peer-reviewed

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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 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.

Description

Peer reviewed: True

Keywords

Research Article, Developmental Biology, Stem Cells and Regenerative Medicine, vinculin, intestinal homeostasis, differentiation, stem cell, mechanotransduction, D. melanogaster

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Conference Name

Journal ISSN

2050-084X

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Publisher

eLife Sciences Publications, Ltd
Sponsorship
Wellcome Trust (Sir Henry Dale Fellowship (206208/Z/17/Z))
Wellcome Trust (PhD student studentship (102175/B/13/Z))
Wellcome Trust (Sir Henry Dale Fellowship to GK(206208/Z/17/Z))