The Role of Perineurial Glia in Peripheral Nerve Regeneration

The vertebrate peripheral nervous system (PNS) encompasses a complex network of nerves responsible for transmitting information between the central nervous system (CNS) and the body. When peripheral nerves are damaged, this flow of vital sensory and motor information is disrupted, and the result can be debilitating. The PNS has the remarkable capability to regenerate, however patients with severe injuries often do not regain full functional recovery, leaving substantial room for improvement in therapies. Although peripheral nerve regeneration has been studied extensively with respect to axons, Schwann cells, and even macrophages, the role of the perineurium in this process is poorly understood.
Here, I present the first detailed characterization of perineurial behavior after nerve injury in a live animal. First, I present my development of a novel assay to study glial responses to nerve transection in live zebrafish larvae. This assay uses laser-mediated nerve transection followed by in vivo time-lapse microscopy. Using this assay, I show that perineurial glia respond to nerve injury with rapid and dynamic changes in behavior. Perineurial glia send highly motile membrane processes toward injury sizes, phagocytize debris, and eventually bridge the gap between proximal and distal nerve stumps. In the absence of these bridges, axon regrowth is impaired, suggesting that perineurial glia are essential for successful regeneration. Finally, I present evidence that perineurial glia communicate and coordinate with Schwann cells and macrophages after injury. This work introduces perineurial glia as active and influential players in the early response to nerve injury.