Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia. Yoichiro Tamori, Wu-Min Deng. Biological Science, Florida State University, Tallahassee, FL.

   Tissue integrity and organ size are finely maintained through removal of aberrant or damaged cells and subsequent compensatory proliferation of the surrounding normal cells, which are induced by mitogenic signals from the dying cells. Little is known, however, about the 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, normal cells can kill and eliminate aberrant but viable neighbors through "cell competition," and resulting lowered cellular density triggers sporadic cellular hypertrophy to repair the tissue. This "compensatory cellular hypertrophy" (CCH) 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 (insulin-like growth factor)-like signaling pathway. It has been shown that hyperplastic overproliferation is induced in neighboring normal cells when apoptotic cells are kept alive by the expression of baculovirus caspase inhibitor, p35, in proliferating imaginal epithlia. Although CCH was observed when sporadic apoptosis was induced in the postmitotic follicular epithelia, the undead cells expressing p35 induced neither overproliferation nor CCH of neighbors. Furthermore, sporadic CCH was observed when a small group of viable cells had a growth defect. Collectively, these results led us to conclude that CCH is sporadically induced by lowered cellular density resulting from cellular growth or viability defects of some cells in the postmitotic epithelium and that apoptosis is not necessary to induce CCH. Our findings are the first identification of cell competition in a postmitotic tissue and of compensatory cellular hypertrophy induced by physical parameters, demonstrating a previously unknown strategy of homeostatic epithelial plasticity.