Identifying a transcriptional program that regulates compensatory proliferation. Joy H Meserve¹, Robert J Duronio². 1) Curriculum in Genetics and Molecular Biology, UNC, Chapel Hill, NC; 2) Departments of Biology and Genetics, UNC, Chapel Hill, NC.

   All animals undergo damage as they develop and age, and many organisms have evolved mechanisms to respond to and repair this damage. One such mechanism is compensatory proliferation, during which cells that are dying following injury will mitogenically signal surrounding cells to increase proliferation and replace lost cells. This process is heavily utilized in damaged precursor cell populations during development and stem cells during adult life. However, many post-mitotic cells appear unable to re-enter the cell cycle and proliferate in response to damage, which hinders regeneration of adult tissues; the reasons for this inability are not well understood. Furthermore, sustained injury in adult tissues leads to cell death which may promote hyperproliferation and the development of cancer. Therefore, it is essential to understand the mechanisms underlying compensatory proliferation, particularly within post-mitotic tissues. In the eye imaginal disc of Drosophila melanogaster, there is a population of post-mitotic, undifferentiated cells that are able to undergo compensatory proliferation. How these cells overcome negative cell cycle regulation and re-enter the cell cycle is currently unknown. We hypothesize that a unique transcriptional program required for compensatory proliferation exists within these post-mitotic eye cells. We are currently testing this hypothesis by characterizing the transcriptional profile in these cells using fluorescence-activated cell sorting (FACS) to isolate the compensatory proliferating population and RNA-seq to identify the transcriptome. Genes that are highly expressed in these cells and not in their non-proliferating counterparts are likely to be involved in compensatory proliferation. We are also carrying out an RNAi screen to identify transcription factors required for compensatory proliferation. The results from these experiments will provide a comprehensive view of compensatory proliferation in a post-mitotic cell population.