Repulsive Epithelial Cues Direct Glial Migration along the Nerve

Most glial cells show pronounced migratory abilities and generally follow axonal trajectories to reach their final destination. However, the molecular cues controlling their directional migration are largely unknown. To address this, we established glial migration onto the developing Drosophila leg imaginal disc as a model. Here, CNS-derived glial cells move along nerves containing motoaxons and sensory axons. Along their path, glial cells encounter at least three choice points where directional decisions are needed. Subsequent genetic analyses allowed uncovering mechanisms that escaped previous studies. Most strikingly, we found that glial cells require the expression of the repulsive guidance receptors PlexinA/B and Robo2 to prevent breaking away from the nerve. Interestingly, the repulsive ligands are presented by the underlying leg imaginal disc epithelium, which appears to push glial cells toward the axon fascicle. In conclusion, nerve formation not only requires neuron-glia interaction but also depends on glial-epithelial communication.