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.
Rhiner
Christa
C
Spanish National Cancer Centre (CNIO), Melchor Fernández Almagro 3, E-28029 Madrid, Spain.
López-Gay
Jesús M
JM
Soldini
Davide
D
Casas-Tinto
Sergio
S
Martín
Francisco A
FA
Lombardía
Luis
L
Moreno
Eduardo
E
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology*; D005110:Extracellular Space / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D038081:Organogenesis / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology; D014921:Wings, Animal / Q000166:cytology / Q000196:embryology*
D015220:Calcium Channels; D029721:Drosophila Proteins; D020033:Protein Isoforms; C543900:fwe protein, Drosophila