Mechanical context defines integrin requirement for maintaining epithelia architecture

Abstract

Epithelial tissues form cohesive sheets of cells anchored to an underlying basement membrane (BM). They are broadly classified as simple or stratified, each fulfilling distinct physiological roles. While mechanisms driving stratification are increasingly well characterized, those safeguarding simple epithelial architecture remain poorly defined. 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, we uncover previously unrecognized integrin-dependent mechanisms esential for preserving simple epithelial integrity. In addition to their known role in orienting cell division, integrins regulate cell reintegration dynamics and modulate surface tension at the cellular level. We further demonstrate that the maintenance of epithelial architecture is governed by mechanisms acting across both cellular and tissue scales. In our model, BM mechanical properties--including stiffness anisotropy--cooperate with integrin-mediated adhesion and tissue geometry to preserve epithelial organization. Given the central role of epithelial disorganization in tumorigenesis, elucidating these mechanical and molecular regulators is critical for understanding epithelial morphogenesis, maintaining tissue homeostasis, and uncovering the early events of cancer progression.