Drosophila SPARC Is a Self-Protective Signal Expressed by Loser Cells during Cell Competition

During development and aging, animals suffer insults that modify the fitness of individual cells. In Drosophila, the elimination of viable but suboptimal cells is mediated by cell competition, ensuring that these cells do not accumulate during development. In addition, certain genes such as the Drosophila homolog of human c-myc (dmyc) are able to transform cells into supercompetitors, which eliminate neighboring wild-type cells by apoptosis and overproliferate, leaving total cell numbers unchanged. Here we have identified Drosophila Sparc as an early marker transcriptionally upregulated in loser cells that provides a transient protection by inhibiting Caspase activation in outcompeted cells. Overall, we describe the unexpected existence of a physiological mechanism that counteracts cell competition during development. [Display omitted] ► The secreted molecule dSPARC is upregulated during cell competition in loser cells ► dSPARC expression prevents the elimination of loser cells by winner cells ► dSPARC specifically inhibits cell competition-induced apoptosis ► dSPARC and the Fwe code act in parallel pathways with opposing roles