The Drosophila caspase DRONC is required for metamorphosis and cell death in response to irradiation and developmental signals

Cell death is essential for eliminating excess cells during development as well as removing damaged cells. While multiple conserved apoptosis pathways involving different cascades of caspases, which are cysteine proteases, have been identified, their regulation in the context of a developing organism is not very well understood. Expression of the Drosophila caspase-9 homolog, DRONC, can be induced by ecdysone, a steroid hormone, which induces metamorphosis. To elucidate the functional role of DRONC during metamorphosis and for cell death during development we have generated and analyzed two loss-of-function alleles of DRONC. We report that DRONC is required for developmentally induced neuroblast cell death and apoptosis in response to X irradiation. DRONC mutants show reduced pupariation even in the presence of high levels of ecdysone and impaired cell death of larval midgut. The levels of ecdysone-inducible transcripts such as E75A and Reaper (Rpr) are normal in the absence of DRONC, suggesting that DRONC acts downstream of these genes. In addition, Reaper and Grim, but not Hid induced apoptosis is sensitive to a reduction of DRONC levels. Our study places DRONC at a central point of convergence for multiple cell death pathways and for the ecdysone pathway regulating metamorphosis.