Gliatrophic and gliatropic roles of PVF/PVR signaling during axon guidance

Abstract

Evidence of molecular and functional homology between vertebrate and Drosophila glia is limited, restricting the power of Drosophila as a model system to unravel the molecular basis of glial function. Like in vertebrates, in the Drosophila central nervous system glial cells are produced in excess and surplus glia are eliminated by apoptosis adjusting final glial number to axons. The underlying molecular mechanisms are largely unknown, as the only gliatrophic pathway known to date in flies is the EGFR and its ligands. The PDGFR signaling pathway plays a major role in regulating oligodendrocyte migration and number in vertebrates. Here, we show that the Drosophila PDGFR/VEGFR homologue PVR is required in midline glia during axon guidance for glial survival and migration, ultimately enabling axonal enwrapment. The midline glia migrate aided by the VUM and the MP1 midline neurons--sources of PVF ligands--and concomitantly interactions with neurons maintain midline glia survival. Upon loss of function for PVF/PVR signaling midline glia apoptosis increases, and gain of function induces supernumerary midline glia. Midline glial cells are displaced towards ectopic sources of PVF ligands. PVR signaling promotes midline glia survival through AKT and ERK pathways. This work shows that the PVR/PDGFR pathway plays conserved gliatrophic and gliatropic roles in subsets of glial cells in flies and vertebrates.