Molecular characterization of cell competition and compensatory cell proliferation in Drosophila. Li He. Genetics, Harvard Medical School, Boston, MA.

   One of the most fascinating questions in biology is how organs achieve and maintain their final sizes, which is continuously regulated by coordinated cell death and proliferation. Two evolutionary conserved and highly correlated mechanisms, cell competition and compensatory cell proliferation, have emerged as playing fundamental roles in this process. Cellular competition is the process by which cells possessing unequal fitness, which can survive if kept alone, compete with each other during tissue growth. Competition between the two cell populations involves active cell killing of the less fit losers by the fitter winners. Activation of apoptosis in the loser cells in turn triggers compensatory proliferation of the winners, thus maintaining proper organ size. Besides the size-control function, cell competition has also been found to maintain the tissue quality by eliminating mutant cells with oncogenesis potential. In addition, deregulation of cell competition may also promote cancer initiation or metastatic colonization. Studies in the past ten years have implicated a number of signaling pathways such as Jun-kinase, Wnt, Hedgehog, Decapentaplegic(Dpp), and growth regulators such as Myc, Yorkie and ribosomal proteins in these processes. However, despite these advances, we still do not fully understand how loser cells are recognized and eliminated and how winner cells are induced to proliferate. Since cell competition and the ability of dying cells to secrete ligands also occur in tissue culture, we propose to first develop system level methodology to characterize the signaling mechanisms of these processes in drosophila tissue culture and verify the result in vivo using a new mosaic RNAi method for twin spot analysis.