The process of cell competition is believed to provide a mechanism to optimise tissue ‘fitness’ during development by eliminating weaker cells from the overall cell population. First described in Drosophila, a number of genes have been linked to cell competition but the precise details of the process are poorly understood. A new study conducted by scientists at the Spanish National Cancer Centre (CNIO), however, has furthered our understanding.
Using a combination of genomic analysis and functional assays, the team investigated how cells of Drosophila wing imaginal discs distinguished ‘winner’ and ‘loser’ cells. They found that six genes were upregulated early in loser cells and five of these encoded cell membrane proteins, suggesting that cell-cell communication is critical in the initial stages of cell competition. One of these membrane proteins, Flower (Fwe), was examined in detail.
Fwe is conserved in multicellular organisms and in the Drosophila study was found to be required and sufficient to label cells as winners or losers. The win/lose decision is mediated by three differentially expressed forms of fwe (fweubi, fweLoseA and fweLoseB) and cells are identified as losers when relative differences in fweubi and fweLose levels are detected – stress conditions that uniformly affect the entire population result in cell survival. Although further work is necessary to elucidate the detail, the team proposes that, in outcompeted cells, the fwe transcript is alternatively spliced and fweLose isoforms are induced at the expense of fweubi. It is likely that downregulation of fweubi and upregulation of fweLose both contribute to establish the lose/win decision.
The cellular tagging by Flower isoforms may have biomedical implications beyond cell competition since imbalances in cell fitness also occur during ageing, cancer formation and metastasis.
The study is published in Developmental Cell.