Integrin diversity enables dynamic adhesion control in a homeostatic epithelium

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 βMys and endoderm-specific βν. ISCs and enteroblasts express only βMys, which pairs with αMew to mediate enteroblast attachment to the basement membrane. In contrast, enterocytes express both βMys and βν; αMew/βν supports ECM adhesion, while βMys pairs with αScab and localises to the basal labyrinth. Enterocytes lacking αMew or βν 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 βν 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.