Apical constriction induces tissue rupture in a proliferative epithelium

• Published in: bioRxiv
• Main Authors: Osswald, Mariana, Barros-Carvalho, Andre, Carmo, Ana M, Loyer, Nicolas, Gracio, Patricia C, Sunkel, Claudio E, Catarina Cf Homem, Januschke, Jens, Morais-De-Sa, Eurico
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 04.03.2022
• Subjects: Actomyosin; Contractility; Epithelium; Light effects; Polarity; Rupture
• DOI: 10.1101/2022.03.02.482459

Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Deregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncovered how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we could modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation rapidly induces apical constriction in non-mitotic cells, producing pulling forces that ultimately detach dividing and neighbouring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, since it was prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side was sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the first in vivo evidence that excessive tissue stress can break the epithelial barrier during proliferation. Competing Interest Statement The authors have declared no competing interest.