Cytonemes coordinate asymmetric signaling and organization in the Drosophila muscle progenitor niche

Asymmetric signaling and organization in the stem-cell niche determine stem-cell fates. We investigated the basis of asymmetric signaling and stem-cell organization using the Drosophila wing-disc that creates an adult muscle progenitor (AMP) niche. We uncovered that AMPs extend polarized cytonemes to contact the disc epithelial junctions and adhere themselves to the disc/niche. Niche-adhering cytonemes localize an FGF-receptor to selectively adhere to the FGF-producing disc and receive FGFs in a contact-dependent manner. Activation of FGF-signaling in AMPs, in turn, reinforces disc-specific cytoneme polarity/adhesion, which maintains their disc-proximal positions. The wing-disc produces two FGFs in distinct zones and restricts their signaling only through cytonemes. Consequently, although both FGFs use the same receptor, their cytoneme-mediated signaling asymmetrically distributes different muscle-specific AMPs into different FGF-producing niches. Loss of cytoneme-mediated adhesion and FGF-signaling promotes AMPs to lose niche occupancy, occupy a disc-distal position, and acquire morphological hallmarks of differentiation. Thus, cytonemes are essential for asymmetric signaling and niche-specific AMP organization.