An epithelial cell destined for apoptosis signals its neighbors to extrudeit by an actin- and myosin-dependent mechanism

Background: Simple epithelia encase developing embryos and organs. Although these epithelia consist of only one or two layers of cells, they must prov ide tight barriers for the tissues that they envelop. Apoptosis occurring w ithin these simple epithelia could compromise this barrier. How, then, does an epithelium remove apoptotic cells without disrupting its function as a barrier? Results. We show that apoptotic cells are extruded from a simple epithelium by the concerted contraction of their neighbors. A ring of actin and myosi n forms both within the apoptotic cell and in the cells surrounding it, and contraction of the ring formed in the live neighbors is required for apopt otic cell extrusion, as injection of a Rho GTPase inhibitor into these cell s completely blocks extrusion. Addition of apoptotic MDCK cells to an intac t monolayer induces the formation of actin cables in the cells contacted, s uggesting that the signal to form the cable comes from the dying cell. The signal is produced very early in the apoptotic process, before procaspase a ctivation, cell shrinkage, or phosphatidylserine exposure. Remarkably, elec trical resistance studies show that epithelial barrier function is maintain ed, even when large numbers of dying cells are being extruded. Conclusions: We propose that apoptotic cell extrusion is important for the preservation of epithelial barrier function during cell death. Our results suggest that an early signal from the dying cell activates Rho in live neig hbors to extrude the apoptotic cell out of the epithelium.