Hid and reaper differentially regulate apoptotic and non-apoptotic executioner caspase activation to control organ size

One of the fundamental questions in developmental biology is how the organ size is controlled. While apoptosis, a type of programmed cell death, has been shown to restrict growth in proliferating tissues such as Drosophila wing imaginal disc, its key effectors, executioner caspases, paradoxically exhibit pro-growth functions. Executioner caspases are activated in some wing disc cells without triggering apoptosis. How non-apoptotic and apoptotic executioner caspase activation (ECA) are coordinated to regulate wing size remains poorly understood. In this study, we utilize two different executioner caspase reporters to monitor the dynamics of apoptotic and non-apoptotic ECA. We show that apoptotic and non-apoptotic ECA exhibit distinct spatiotemporal patterns during wing disc development, with non-apoptotic ECA prevalent in the proximal region of younger discs and apoptosis enriched in the distal region of older discs. Furthermore, we demonstrate that the non-apoptotic and apoptotic ECA are regulated by different pro-apoptotic genes. Non-apoptotic ECA depends on reaper (rpr), while apoptosis requires head involution defective (hid). In younger discs, rpr-induced non-apoptotic ECA promotes wing growth. As the disc ages, hid triggers strong ECA that leads to apoptosis, thereby refining the final wing size. Our work elucidates the mechanism regulating divergent cell fates following ECA and how they are coordinated to control organ size.