Repeated vital imaging reveals Schwann cells induce and guide nerve sprouting and regeneration of neuromuscular junctions

Terminal Schwann cells (TSCs) normally sit above the endplate and cover the nerve terminal branches with their processes. However, following denervation, they extend long processes beyond the boundaries of the endplate (Reynolds and Woolf, 1992). Previous results conducted as static observations, showed that TSCs play an important role in the restoration of the synapse at the neuromuscular junction after nerve injuries by extending processes (Son and Thompson, 1995a,b). However, we still do not know the precedence of TSCs in muscle reinnervation following nerve injury and what happens to other synaptic components. These questions are addressed in this dissertation. In Chapter 2, I report that TSCs extend processes in response to denervation and these processes guide regenerating axons to grow beyond the endplate area. Furthermore, Schwann cells also cause formation of polyneuronal reinnervation by guiding axons over Schwann cell processes and endoneurial tubes. Finally, withdrawal of TSC processes following denervation induces AChR loss long-term following nerve regeneration. In Chapter 3, I report that TSCs grow long processes at denervated endplates following partial denervation and in some cases these processes interconnect with innervated endplates. Here the TSCs induce and guide terminal sprouts. Schwann cells in endoneurial tubes are able to guide nodal sprouts, suggesting Schwann cells at both nerve terminals and endoneurial tubes can guide nerve sprouting. Taken together, these results show Schwann cells are important for synapse formation and maintenance during nerve regeneration.