Directional cues are essential for orienting cells during tissue morphogenesis and repair. In peripheral nerve regeneration, Schwann cells (SCs) align longitudinally in the nerve bridge to guide axonal pathfinding, but the mechanisms are not fully understood. We show here that after nerve injury, activated SCs up-regulate the guidance receptor Plexin-B1, enabling membrane plasticity required for SC polarization and longitudinal alignment along the axons. Aligned axon-SC provides positional cues