Identification and verification of genes involved in apoptosis-induced proliferation in Drosophila. Yun Fan^1,2, Andreas Bergmann². 1) School of Biosciences, University of Birmingham, Birmingham, United Kingdom; 2) Cancer Biology, UMass Medical School, Worcester, United States.

   Recent work in several model organisms has revealed that apoptotic cells are able to stimulate neighboring surviving cells to undergo additional proliferation, a phenomenon termed apoptosis-induced proliferation. This process depends critically on apoptotic caspases such as Dronc, the Caspase-9 ortholog in Drosophila, and may have important implications for tumorigenesis and tissue regeneration. While it is known that Dronc can induce the activity of Jun N-terminal kinase (JNK) for apoptosis-induced proliferation, the mechanistic details of this activation are largely unknown. It is also controversial if JNK activity occurs in dying or in proliferating cells. Signaling molecules of the Wg and Dpp families have been implicated in apoptosis-induced proliferation, but it is unclear if they are the only ones. To address these questions, we have developed an efficient assay for screening and identification of genes that regulate or mediate apoptosis-induced proliferation. We have identified a subset of genes acting upstream of JNK activity. We also demonstrate that major JNK activation occurs autonomously in apoptotic cells. Finally, in a pilot screen we identified signaling by the EGFR pathway as important for apoptosis-induced proliferation. Interestingly, requirement of EGFR signaling is also verified in another regenerative assay we developed further suggesting a link between apoptosis-induced proliferation and tissue regeneration. These data thus underscore the importance of genetic screening and promise an improved understanding of the mechanisms of apoptosis-induced proliferation.