Abstract
In Drosophila melanogaster larval epithelial tissues, cells containing mutations in the apico-basal polarity protein, Scrib, are eliminated by cell competition when surrounded by wild-type cells. In scrib mutant cells, signaling mediated by the receptor-type tyrosine phosphatase Ptp10D upon engagement with its ligand Sas in the surrounding wild-type cells triggers cell competition via EGFR-Ras pathway inhibition and JNK pathway activation, which induces apoptosis of the mutant cells. Here, we investigate whether overexpression of RhoGEF2 (RhoGEF2OE), which induces Rho signaling and affects actin cytoskeleton regulators, acts similarly to Scrib depletion in cell competition. We show that RhoGEF2OE cells are eliminated when surrounded by wild-type cells and that Ptp10D knockdown increases RhoGEF2OE clone growth. Mechanistically, in clones moderately overexpressing RhoGEF2OE, Ptp10D knockdown rescued cell elimination by reducing Hippo signaling. Additionally, mutations in the apical cell polarity protein, Crb, partially rescued the elimination of RhoGEF2OE clones. In this setting, in which RhoGEF2OE is highly overexpressed, JNK and Hippo signaling were elevated whereas EGFR-Ras signaling was reduced, and crb loss normalized these pathways. Thus, RhoGEF2OE leads to clone elimination dependent on Crb, Ptp10D and Hippo signaling.
