Tissue Repair through Cell Competition and Compensatory Cellular Hypertrophy in Postmitotic Epithelia

In multicellular organisms, tissue integrity and organ size are maintained through removal of aberrant or damaged cells and compensatory proliferation. Little is known, however, about this homeostasis system in postmitotic tissues, where tissue-intrinsic genetic programs constrain cell division and new cells no longer arise from stem cells. Here we show that, in postmitotic Drosophila follicular epithelia, aberrant but viable cells are eliminated through cell competition, and the resulting loss of local tissue volume triggers sporadic cellular hypertrophy to repair the tissue. This “compensatory cellular hypertrophy” is implemented by acceleration of the endocycle, a variant cell cycle composed of DNA synthesis and gap phases without mitosis, dependent on activation of the insulin/IGF-like signaling pathway. These results reveal a remarkable homeostatic mechanism in postmitotic epithelia that ensures not only elimination of aberrant cells through cell competition but also proper organ-size control that involves compensatory cellular hypertrophy induced by physical parameters. •Cell competition occurs in the postmitotic epithelium•Compensatory cellular hypertrophy (CCH) as a tissue repair mechanism•CCH is implemented by acceleration of the endoreplication cycle•Loss of local tissue volume triggers sporadic epithelial CCH over a long range Tamori and Deng show that cell competition occurs in postmitotic epithelia to remove aberrant cells. Their studies also reveal that a loss of local tissue volume resulting from cell death or reduced cell size triggers compensatory cellular hypertrophy sporadically throughout the epithelium to ensure tissue homeostasis.