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Fernandez-Espartero, C. H.

Publications and source records attributed to Fernandez-Espartero, C. H..

2 recordsLinked to original sources

Integrin loss and tissue mechanics trigger progressive disruption of simple epithelial

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.

cell biology↗

Mechanical context defines integrin requirement for maintaining epithelia architecture

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.

cell biology↗