Epithelial repair is a two-stage process driven first by dying cells and then by their neighbours

Abstract

Epithelial cells maintain an essential barrier despite continuously undergoing mitosis and apoptosis. Biological and biophysical mechanisms have evolved to remove dying cells whilst maintaining that barrier. Cell extrusion is thought to be driven by a multicellular filamentous actin ring formed by the neighbouring cells, with its contraction providing the mechanical force for extrusion, with little or no contribution from the dying cell. We use live confocal imaging, providing time-resolved 3D observations of actomyosin dynamics to reveal new mechanical roles for dying cells in their own extrusion from monolayers. Dying cell clearance could be subdivided into two-stages. The first, previously unidentified, stage was driven by the dying cell, which exerted tension on its neighbours through the action of a cortical contractile F-actin and myosin ring at the cell apex. The second stage, consistent with previous studies, was driven by a multicellular F-actin ring in the neighbouring cells that moved from the apical to the basal plane to extrude the dying cell. Critically, these data reinstate the dying cell as an active physical participant in cell extrusion rather than an innocent bystander.