Integrin loss and tissue mechanics trigger progressive disruption of simple epithelial

Abstract

Simple epithelia form cohesive sheets anchored to a basement membrane (BM), yet the mechanisms that preserve their monolayered architecture remain poorly understood. Here, we address this knowledge gap using the simple follicular epithelium of Drosophila as a model. Combining live imaging, quantitative image analysis, manipulation of BM mechanical properties and biophysical measurements, our results provide evidence supporting the role of integrins in orienting cell division in vivo. They also reveal two previously unrecognized integrin functions essential for epithelial integrity: promoting timely reintegration of displaced cells following non-planar divisions and modulating junctional tension. These activities underpin a stepwise model of epithelial disruption upon integrin removal. An initial ectopic layer arises from altered division orientation and delayed reintegration. Within this layer, integrin-mutant cells exhibit exacerbated defects in both processes, along with increased junctional tension, which together drive progressive epithelial disruption leading to multilayering. BM mechanical properties further modulate these processes, shaping regional susceptibility to disruption. Together, our work defines how integrin-mediated adhesion and BM mechanics maintain epithelial architecture, while revealing discrete intermediate stages of breakdown with potential relevance to epithelial disorganisation in diseases such as cancer.