Peripheral nerve injuries are devastating and can result in functional loss, deformity, and paralysis. Clinical outcome is related to the period of target muscle denervation, with poor functional results after prolonged denervation. After a period of 12-18 months after complete nerve injury, integration between nerve and muscle is no longer possible. Strategies to protect the muscle target during the denervation period would improve outcomes after motor nerve injury and may allow integration between nerve and muscle beyond the 18 month window. Terminal Schwann cells (tSCs) are the glial cells located at the neuromuscular junction, or at the muscle target. These cells have been relatively understudied compared to other Schwann cells. In this proposal we will utilize genetic and morphologic techniques in multiple in vivo models to identify the contributions of tSCs to synaptic function and neuromuscular junction (NMJ) reinnervation, and we will assess the relationship of Vegf to the tSC response to nerve injury. In addition, we will identify unique genetic markers of tSCs, which will further propel the tools available to study tSCs. The data generated from this proposal will fuel an innovative area of tSC investigation that may provide novel information for translational applications to peripheral motor nerve injuries. During the four-year period of support provided by the mentored career development award, Dr. Snyder- Warwick will advance her scientific investigation skills through mentored research, formal coursework, seminars, and group discussions. Her assembled team of expert mentors within the academically generous and exceptional scientific environment at Washington University will enable successful completion of her project and career goals. The training provided by the K08 award will foster her career goal of becoming a successful, independent, academic surgeon-scientist with a focus on peripheral nerve reconstruction. The data generated from the proposed studies will provide a sound foundation for transition to independent investigation and R-level NIH funding.
In this study, we investigate terminal Schwann cells, which are specialized cells located at the interface between motor nerves and muscle. We propose to determine the roles of these cells in normal function and after motor nerve injury. These studies may help to suggest new strategies for treatment of peripheral nerve injuries.
