ROCK-mediated junctional remodelling preserves barrier function in a developing epithelium during hypoxia

Abstract

Epithelia contribute to organismal homeostasis by functioning as selectively permeable barriers. Being avascular, epithelia are particularly vulnerable to hypoxia. Yet how developing epithelia adapt to preserve tissue integrity under hypoxic conditions remains elusive. Here, we show that in bilayered zebrafish epidermis hypoxia disrupts epithelial architecture reversibly, but preserves tight junction-mediated barrier function. ROCK maintains the tight apico-cortical localisation of active Non-muscle myosin-II (pNM-II) to mediate a squamous-to-cuboidal shape transition in epithelial cells under hypoxia. It further suppresses Crb3-dependent local force imbalance that otherwise results in cell delamination and cell-rosette formation. Importantly, we identify ROCK as a regulator that promotes barrier function maintenance specifically under hypoxia. Our genetic analyses demonstrate that ROCK primarily coordinates junctional remodelling to maintain barrier function during hypoxia while actomyosin contractility may foster the junctions secondarily. We propose that under an energy constrained hypoxic environment, dismantling E-cadherin based adhesion and augmenting ROCK-dependent barrier function in a developing epithelium ensures organism survival allowing recovery when normoxic conditions resume.