Perineurial Glia Are Essential for Motor Axon Regrowth Following Nerve Injury

Development and maintenance of the peripheral nervous system (PNS) are essential for an organism to survive and reproduce, and damage to the PNS by disease or injury is often debilitating. Remarkably, the nerves of the PNS are capable of regenerating after trauma. However, full functional recovery after nerve injuries remains poor. Peripheral nerve regeneration has been studied extensively, with particular emphasis on elucidating the roles of Schwann cells and macrophages during degeneration and subsequent regeneration. In contrast, the roles of other essential nerve components, including perineurial glia, are poorly understood. Here, we use laser nerve transection and in vivo, time-lapse imaging in zebrafish to investigate the role and requirement of perineurial glia after nerve injury. We show that perineurial glia respond rapidly and dynamically to nerve transections by extending processes into injury sites and phagocytizing debris. Perineurial glia also bridge injury gaps before Schwann cells and axons, and we demonstrate that these bridges are essential for axon regrowth. Additionally, we show that perineurial glia and macrophages spatially coordinate early debris clearance and that perineurial glia require Schwann cells for their attraction to injury sites. This work highlights the complex nature of cell-cell interactions after injury and introduces perineurial glia as integral players in the regenerative process.