Glial cells are important for organising and protecting axons in the nervous system. Although myelinated ensheathment of axons has been well-studied, the majority of wrapping in the vertebrate peripheral nervous system is by non-myelinating multi-axon ensheathment, which is less well understood. Now, Megan Corty, Marc Freeman and colleagues study specialised axon-associated wrapping glia in Drosophila, which are analogous to the Remak Schwann cells that ensheath unmyelinated axons in vertebrates. When selectively ablating the wrapping glia, the authors observe impaired crawling behaviour in larvae, indicating that the glia are required for normal circuit formation. Using an RNAi screen and confirmatory CRISPR mutants, the authors discover that Discoidin domain receptor (Ddr), a cell surface receptor tyrosine kinase, is required for normal glia morphology and axon ensheathment of larval nerves. A strong genetic interaction with Multiplexin, a type XV/XVIII collagen, suggests that Ddr functions as collagen receptor in the wrapping glia. In adult flies, glial Ddr is dispensable for ensheathment of axons, but is required for normal axon growth and to maintain healthy sensory neurons. Together, these data demonstrate the essential role of wrapping glia in ensheathment, survival and growth in the nervous system, in a Ddr-dependent manner.
