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bioRxiv · 10.64898/2026.08.13.744583

Integrin diversity enables dynamic adhesion control in a homeostatic epithelium

Abstract

Homeostatic epithelia must balance stem cell maintenance, progenitor differentiation, and clearance of damaged cells while preserving barrier integrity. We investigated how integrin- ECM adhesion is regulated in the Drosophila midgut, a homeostatic epithelium with basal stem cells. The midgut expresses two beta integrins: ubiquitous {beta}Mys and endoderm-specific {beta}{nu}. ISCs and enteroblasts express only {beta}Mys, which pairs with Mew to mediate enteroblast attachment to the basement membrane. In contrast, enterocytes express both {beta}Mys and {beta}{nu}; Mew/{beta}{nu} supports ECM adhesion, while {beta}Mys pairs with Scab and localises to the basal labyrinth. Enterocytes lacking Mew or {beta}{nu} detach and are apically extruded, but this phenotype is rescued when the corresponding integrin is removed from the entire epithelium. Thus, enterocytes compete for basement membrane adhesion, with less adhesive cells being eliminated by their neighbours. In {beta}{nu} homozygotes, enteroblasts expand basally and adopt a migratory-like morphology. We propose that integrin-mediated competition for ECM adhesion is a general phenomenon that functions in the midgut to promote enterocyte extrusion, which stimulates the migration of nearby enteroblasts to maintain gut homeostasis.

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Chen, J., Sugita, D., Allgeyer, E., Saumya, D., Shunmugam, D., St Johnston, D.. 2026-08-20. Integrin diversity enables dynamic adhesion control in a homeostatic epithelium. https://doi.org/10.64898/2026.08.13.744583

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