Abstract
Glial spatial organization is critical for neural repair after spinal cord injury (SCI). In response to injury, reactive astrocytes extend hypertrophic processes to corral the lesion core and sequester debris and inflammatory cells. How these long, arborized processes remain intact, and how astrocytes avoid collisions to assemble a glial bridge to guide axon pathfinding across lesion site remains unclear. Here we identify the guidance receptor Plexin‑B1 as a regulator of membrane integrity, process plasticity, and astrocyte alignment. Live‑cell imaging reveal that Plexin‑B1 deletion triggers membrane shedding and slows extension and retraction of astrocytic processes. The loss of astrocyte agility disrupts contact‑dependent avoidance, leading to disorganized astrocytes and misguided axons in vitro and in vivo. Mice with astrocyte‑specific Plexin‑B1 deletion show defective glial border, enlarged lesions, inflammatory spill‑over, and dysregulated astrocyte-microglia signaling. These defects result in impaired axon regeneration and poorer functional recovery after spinal‑cord injury. Thus, Plexin‑B1-mediated agility of astrocyte processes safeguards membrane integrity and spatial alignment, enabling effective wound corralling and axon pathfinding during neural repair following SCI.