We are uncovering how necrotic injury drives proliferation through unexpected caspase activity in surviving cells. Building on our discovery of what we initially called necrosis-induced apoptosis (NiA), we found that some NiA cells resist death, maintaining active initiator caspases such as Dronc while escaping full apoptosis. These Necrosis-induced Caspase-Positive (NiCP) cells persist within regenerating tissue, acting as a source of non-apoptotic caspase signaling that stimulates cell division late in regeneration. This Dronc-dependent proliferation occurs independently of JNK, ROS, or classical mitogens like WNT and EGF, defining a previously unknown regenerative mechanism.

Our findings reveal that caspases—traditionally seen as death effectors—can function as pro-regenerative signals when activated by necrosis. By distinguishing between apoptotic and non-apoptotic caspase roles, we are redefining how damaged tissues harness cell-death machinery to rebuild. Understanding these pathways may uncover therapeutic avenues to enhance recovery from necrotic injuries in both model systems and human disease.