Mechanisms of cell competition in Drosophila

Abstract

Cell competition is a kind of cell-cell interaction, in which one group of cells grow at the expense of the other cell population. Cell competition may be involved in growth control, tumorigenesis and tissue replacement. The goal of my study in this thesis is to genetically analyze the mechanism of cell competition. I have employed the Drosophila wing imaginal disc and eye as model organs, and focused on cell competition between wild type cells (+/+, winner cells) and Minute mutant cells (M/+, loser cells). I found that cell death, which is essential to cell competition, occurs mostly in M/+ cells touching +/+ cells. M /+ cell corpses are engulfed by neighboring +/+ epithelial cells. Unexpectedly, engulfment activity in +/+ cells is required for cell death induction. Several engulfment genes, including draper, Wiskott-Aldrich syndrome protein, myoblast city, and rac1, and the phosphatidyl-serine receptor are required in +/+ cells for killing M/+ cells. Wild type cells can themselves be killed by cells with elevated engulfment activity. Through analyzing the requirement of several candidate cell death components for competitive cell death, my results confirmed the essentiality of a gene or genes deleted by the deficiency H99 to such cell death. However, competitive cell death appears to use an unusual cell death machinery not involving Dronc activation, nor depending on Dredd. By contrast, this cell death is completely abolished recessively by two mutations on chromosome 3L, which are viable and do not affect growth and the developmental cell death in the Drosophila pupal retina. My study also indicated that the compensatory proliferation in cell competition occurs without using Dronc. In conclusion, this study indicated that cell death in cell competition is not a cell-autonomous effect in loser cells; but depends on engulfment activity of winner cells. Such non-autonomous cell-killing could occur between cells without growth differences and may employ a novel cell death machinery. I propose that cell competition is a phagocytic process, in which growth defects are sensed and lead to engulfment and killing by neighboring cells.