Fernandes, M.;Kaushik, A.;Sonawane, M.

Oxygen is indispensable for survival in aerobic organisms, necessitating mechanisms to sense and respond to fluctuations in oxygen availability. Physiological processes such as early development, proceeds in an oxygen-sensitive environment and this appears conserved across vertebrate evolution. Owing to their avascular nature epithelial tissues routinely experience hypoxia but the epithelial responses to hypoxia and the underlying adaptive molecular regulation remains to be fully understood. We used the bilayered epidermis of Zebrafish embryos to ask how a developing epithelium responds to and copes with hypoxia. We show that under hypoxic conditions, despite the changes in cell morphologies, disruption in E-cadherin polarisation and the presence of intercellular gaps in the outer epidermal layer, the tight junctions are maintained. Our data indicate that ROCK (Rho-associated kinase) mediates the change in cell morphology and the maintenance of barrier function via non-muscle Myosin-II (NM-II). Furthermore, a high level of NM-II activity is essential to suppress Crb3-dependent cell delamination and apoptosis under hypoxia. Genetic perturbations reveal that neither increasing levels of active NMII nor augmenting tight junctions alone improves barrier function defects, indicating both these ROCK-dependent processes are necessary to maintain the barrier function under hypoxia. Our study uncovers the hitherto unappreciated importance of ROCK signaling in the maintenance of epithelial architecture and barrier function in a developing epithelium, ensuring organism survival.