Cholinergic and Glutamatergic Axons Differentially Require Glial Support in the Drosophila PNS

ABSTRACT In vertebrates, there is a differential interaction between peripheral axons and their associated glial cells. While large‐caliber axons are covered by a myelin sheath, small‐diameter axons are simply wrapped in Remak fibers. In peripheral nerves of Drosophila larvae, axons are covered by wrapping glial cell processes similar to vertebrate Remak fibers. Whether differences in axonal diameter influence the interaction with glial processes in Drosophila has not yet been analyzed. Likewise, it is not understood whether the modality of the neuron affects the interaction with the wrapping glia. To start to decipher the mechanisms underlying glial wrapping, we employed APEX2 labeling in larval filet preparations. This allowed us to follow individual axons of defined segmental nerves at ultrastructural resolution in the presence or absence of wrapping glia. Using these tools, we first demonstrate that motor axons are larger compared to sensory axons. Sensory axons fasciculate in larger groups than motor axons, suggesting that they do not require direct contact with wrapping glia. However, unlike motor axons, sensory axons show length‐dependent degeneration upon ablation of wrapping glia. These data suggest that Drosophila may help to understand peripheral neuropathies caused by defects in Schwann cell function, in which a similar degeneration of sensory axons is observed.