Control of growth and cell competition by dMyc in Drosophila melanogaster.

摘要

Cell competition is one of many intrinsic controls on cell proliferation and survival in the imaginal discs of D. melanogaster. Currently it is operationally defined: its hallmark is that the growth and contribution of a cell clone to the adult is decreased when surrounded by a genetically different population. A classic example of cell competition is that Minute (M/+) clones fail to persist in the presence of wildtype neighbors. How these events are initiated and carried out, and whether cell competition is important to the wing's intrinsic size control, is not established.; To understand the differences that lead to cell competition between neighbors in the wing imaginal disc, we over-expressed several genes critical for animal growth. We show that cells expressing different levels of Drosophila Myc (dMyc) compete with one another, resulting in poor contribution to the wing by cells expressing less dMyc than their neighbors. We also present evidence that apoptosis is responsible for the poor growth of such cells, and further, that cell death is necessary to ensure appropriate wing size in these conditions.; To discover molecular mechanisms underlying cell competition, we have identified genes expressed by competing cell populations and, using mutations, tested the requirement for candidate genes. Specifically, we isolated competing cell populations from two competitive contexts: mosaic wing discs containing dMyc-expressing clones, and M/+ mosaics containing wildtype clones. We describe a small set of transcripts that are up-regulated by cells out-competed in both contexts, which could form the basis of a "molecular signature" of cells eliminated by competition. Finally, we investigated the roles of candidate genes eiger and Drosophila p53 ( dp53) in cell competition between dMyc-expressing and wildtype cells. Expression of eiger, a TNF homolog, is up-regulated in cells out-competed by dMyc-expressing clones. We show that eiger function contributes to the poor growth of these cells, but its loss is not sufficient to prevent cell competition. dp53, a homolog of the p53 tumor suppressor, is expressed highly by dMyc-expressing cells. We find that dp53 is required, specifically in competing populations, for the survival of cells expressing higher levels of dMyc than their neighbors.