Wingless promotes EGFR signaling in follicle stem cells to maintain self-renewal.

Adult stem cell niche boundaries must be precisely maintained to facilitate the segregation of stem cell and daughter cell fates. However, the mechanisms that govern this process in epithelial tissues are not fully understood. In this study, we investigated the relationship between two signals, Wnt and EGFR, that are necessary for self-renewal of the epithelial follicle stem cells (FSCs) in the Drosophila ovary, but must be downregulated in cells that have exited the niche to allow for differentiation. We found that Wingless produced by inner germarial sheath (IGS) cells acts over a short distance to activate Wnt signaling in FSCs, and that movement across the FSC niche boundary is limited. In addition, we show that Wnt signaling functions genetically upstream of EGFR signaling by activating the expression of the EGFR ligand, Spitz, and that constitutive activation of EGFR partially rescues the self-renewal defect caused by loss of Wnt signaling. Collectively, our findings support a model in which the Wnt and EGFR pathways operate in a signaling hierarchy to promote FSC self-renewal.