Flower Forms an Extracellular Code that Reveals the Fitness of a Cell to its Neighbors in Drosophila

Cell competition promotes the elimination of weaker cells from a growing population. Here we investigate how cells of Drosophila wing imaginal discs distinguish “winners” from “losers” during cell competition. Using genomic and functional assays, we have identified several factors implicated in the process, including Flower (Fwe), a cell membrane protein conserved in multicellular animals. Our results suggest that Fwe is a component of the cell competition response that is required and sufficient to label cells as “winners” or “losers.” In Drosophila, the fwe locus produces three isoforms, fwe ubi, fwe Lose-A , and fwe Lose-B . Basal levels of fwe ubi are constantly produced. During competition, the fwe Lose isoforms are upregulated in prospective loser cells. Cell-cell comparison of relative fwe Lose and fwe ubi levels ultimately determines which cell undergoes apoptosis. This “extracellular code” may constitute an ancient mechanism to terminate competitive conflicts among cells. ► Flower (Fwe) is a conserved cell membrane protein ► During cell competition in fly imaginal discs, Fwe determines “winners” and “losers” ► A ubiquitous Fwe isoform promotes cell survival ► Fwe isoforms produced only by “loser” cells induce cell death