Project Summary
Extrusion of cells from epithelia occurs in response to apoptosis, cell crowding or epithelial-mesenchymal transitions. Extrusion poses a challenge to epithelial barrier function and thus requires morphogenetic programs coordinating contractility and adhesion between the extruding and surrounding cells. We recently described that enhanced actomyosin contractility at lateral cell interfaces induces extrusion and apoptosis of aberrantly specified cells and thus may represents a potential tumor suppression mechanism in epithelia. We will investigate which cell surface signals mediate recognition of aberrantly specified cells, which cellular machineries execute and coordinate extrusion between neighboring cells and how the morphogenetic programs of apoptotic and live cell extrusion may differ. Specifically, we will test the role of Eph-Ephrin, Tartan/Capricious, Robo/Slit and Sas/Ptp10D signals in inducing lateral contractility, the role of punctate E-cadherin spot junctions in coordinating lateral contractility between neighboring cells and the role of mechano-sensitive Hippo/YAP/TAZ signaling in apoptotic extrusion. Ultimately, we will transfer knowledge generated in Drosophila epithelia to mammalian models thereby elucidating conserved mechanisms of physiological and pathological extrusion processes.
