Apoptosis-resistant cells drive compensatory proliferation via cell-autonomous and non-autonomous functions of the initiator caspase Dronc.

ABSTRACT: Caspases are best known for promoting apoptosis, yet their role in tissue regeneration by compensatory proliferation remains unclear. Using Drosophila wing discs and a delayed reporter for the initiator caspase-9 ortholog Dronc activity, we identify two apoptosis-resistant epithelial cell populations that mediate regeneration after ionizing radiation: Dronc-activating (DARE) and non-activating (NARE) cells. Dronc activity in DARE cells, independent of Dark and effector caspases, drives regeneration both cell-autonomously and non-cell-autonomously. The TNFR in DARE cells, Wengen, likely activated by ROS, strongly promotes DARE proliferation, while TNF/Eiger and TNFR Grindelwald moderately suppress it. Downstream, p38 MAPK is the main signaling essential for DARE and NARE cell proliferation.

SUBMITTER: Braun T 

PROVIDER: S-EPMC12678810 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature