Nonlethal functions of caspases as guardians of epithelial tissue homeostasis following stress in Drosophila

The last two decades have seen a rapid expansion in the number of discoveries and studies investigating different paradigms of caspase-dependent non-lethal cellular processes (CDPs). Applying ionizing radiation to Drosophila larvae, revealed different functions of caspases acting to maintain epithelial tissue homeostasis following stress. 1) Irradiation of larvae that are severely compromised for caspase activity revealed a phenomenon in which epithelial cells of the imaginal discs gain high migratory and invasive capacities. We termed this phenomenon irradiation-induced cell migration (ICM), although we found that it also occurs spontaneously during development. Importantly, caspase activity that is far below the threshold required to trigger cell death, potently inhibits ICM. 2) We recently discovered that some imaginal disc cells remain highly resistant to ionizing radiation, despite activating the initiator caspase-9 ortholog, Dronc. Accordingly, we found that these cells do not activate the effector caspases, but instead proliferate and occupy almost the entire tissue, implying that they may serve as a reservoir for compensatory proliferation following stress. 3) Following irradiation of wild-type larvae, many of the imaginal disc cells rapidly acquire a phagocytic fate in a somewhat stochastic manner. We now provide evidence that cells which first reach the lethal threshold of caspase activity, dictate survival and phagocytic fate acquisition in neighboring cells. I will present our most recent data about one or more of these phenomena