The role of Schwann cell-axon interaction in peripheral nerve regeneration

After peripheral nerve injury, Schwann cells are released from the degenerating nerve, dedifferentiated, and then actively participate in axonal regeneration. Dedifferentiated Schwann cells, together with macrophages, are involved in eliminating myelin debris, forming bands of Büngner that provide pathways for regenerating axons, and redifferentiating for remyelination. Activation of Erk1/2 and c-Jun was shown to induce stepwise repair programs in Schwann cells, indicating that plastic changes in Schwann cell activity contribute to interaction with axons for regeneration. Schwann cell β1 integrin was identified to mediate the Cdc2-vimentin pathway and further connect to adaptor molecules in the growth cone of regenerating axons through the binding of extracellular matrix (ECM) proteins. Timely interaction between Schwann cells and the axon (S-A) is critical to achieving efficient axonal regeneration because the delay in S-A interaction results in retarded nerve repair and chronic nerve damage. By comparing with the role of Schwann cells in developing nerves, this review is focused on cellular and molecular aspects of Schwann cell interaction with axons at the early stages of regeneration.