Characterization of the cellular and molecular mechanisms that drive perineurial glial bridging after spinal motor nerve injury in zebrafish

Spinal motor nerves are essential for proper organismal locomotion and survival. Motor nerves consist of bundles of motor axons ensheathed by layers of connective tissue and supporting glial cells. Remarkably, in most vertebrates these motor nerves are able to naturally regenerate following injury, though full functional recovery in mammals is limited. The same glial cells that support the motor nerve during development are activated to allow for efficient and effective regeneration. However, the cellular and molecular interactions that underlie successful motor nerve regeneration remain poorly understood. Studies have classically focused on the regenerative responses of Schwann cells and macrophages; however, little is known about the injury responses of other cells that make up the motor nerve. Recently, studies from our lab identified that in the early hours following spinal motor nerve injury in zebrafish, perineurial glia form a glial bridge across the injury site and phagocytose axonal debris. Though perineurial glia are essential for successful motor nerve development and regeneration after injury, very little is known about their injury response. In this dissertation, using zebrafish as a model organism, I present the first known signaling pathway to drive perineurial glial bridging after spinal motor nerve injury, explore cellular interactions between perineurial glia and Schwann cells, and establish tools for future studies to continue to elucidate the signals that drive successful regeneration. This work fills gaps in our knowledge about the cellular and molecular interactions that occur between essential glial cells to drive injury responses that are necessary for successful motor nerve regeneration and presents potential targets for future therapeutics.