
Necrosis-induced caspase activation in cells distant from the injury site (NiA) promotes regenerative proliferation in the Drosophila wing disc through a novel non-apoptotic function of the initiator caspase Dronc, independent of established Apoptosis-induced Proliferation (AiP) mechanisms.


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Tissue necrosis is a devastating complication for many human diseases and injuries. Unfortunately, our understanding of necrosis and how it impacts surrounding healthy tissue – an essential consideration when developing methods to treat such injuries – has been limited by a lack of robust genetically tractable models. Our lab previously established a method to study necrosis-induced regeneration in the Drosophila wing imaginal disc, which revealed a unique phenomenon whereby cells at a distance from the injury upregulate caspase activity in a process called Necrosis-induced Apoptosis (NiA) that is vital for regeneration. Here we have further investigated this phenomenon, showing that NiA is predominantly associated with the highly regenerative pouch region of the disc, shaped by genetic factors present in the presumptive hinge. Furthermore, we find that a proportion of NiA fail to undergo apoptosis, instead surviving effector caspase activation to persist within the tissue and stimulate reparative proliferation late in regeneration. This proliferation relies on the initiator caspase Dronc, and occurs independent of JNK, ROS or mitogens associated with the previously characterized Apoptosis-induced Proliferation (AiP) mechanism. These data reveal a new means by which non-apoptotic Dronc signaling promotes regenerative proliferation in response to necrotic damage.

### Competing Interest Statement

The authors have declared no competing interest.

Regeneration following tissue necrosis is mediated by non-apoptotic caspase activity

necrosis-induced-caspase-activation-promotes-regenerative-proliferation-in-drosophila-wing-discs


Necrosis-Induced Caspase Activation Promotes Regenerative Proliferation in Drosophila Wing Discs
