Moreno and colleagues used D. melanogaster imaginal discs to study potential initiators of competition. They generated clones that consisted of wild-type cells surrounded by MYC-overexpressing 'supercompetitors' that can outcompete the wild-type cells. Microarray analysis and fluorescence in situ hybridization allowed them to identify six genes that were upregulated at an early time point in the loser wild-type cells. Five of these genes encoded cell membrane proteins, suggesting that cell–cell communication is important in the early stages of cell competition.
One of the six loci encodes Flower (FWE), which multimerizes to form calcium channels and may be important during endocytosis. Alternative splicing generates three FWE isoforms that differ in their extracellular carboxyl termini. The authors found that one isoform (fweubi) was ubiquitously expressed in imaginal discs, whereas the other two (fweLose-A and fweLose-B) were specifically induced in loser cells in the presence of competition. Differential expression of fwe isoforms seems to be crucial for triggering apoptosis: knockdown of the fweLose isoforms protected outcompeted clones from death, whereas overexpression of these isoforms led to apoptosis in wild-type clones. Intriguingly, ubiquitous expression of fweLose did not lead to apoptosis or any obvious defect, which suggests that initiation of apoptosis by fweLose expression is not cell autonomous and that interpretation of the differences in FWE expression — which serves as an extracellular code for cells to compare their relative fitness — by neighbouring cells is needed to trigger death. Competition for survival and growth factors and morphogens seems to be important in determining FWE isoform expression, as cells deprived of these factors express the Lose isoforms at the expense of FWEubi.
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