Signals regulating myelination in peripheral nerves and the Schwann cell response to injury

- The Gpr126 and Neuregulin 1 pathways coordinately regulate the initiation of myelination.
- Different mechanisms regulate the initiation, maturation, and maintenance of myelin.
- c-Jun regulates the Schwann cell response to axonal injury and mediates repair.
- MAPK signaling has dual roles in both myelination and Wallerian degeneration.
- Novel signaling mechanisms are emerging that mediate remyelination.

In peripheral nerves, Schwann cells form myelin, which facilitates the rapid conduction of action potentials along axons in the vertebrate nervous system. Myelinating Schwann cells are derived from neural crest progenitors in a step-wise process that is regulated by extracellular signals and transcription factors. In addition to forming the myelin sheath, Schwann cells orchestrate much of the regenerative response that occurs after injury to peripheral nerves. In response to injury, myelinating Schwann cells dedifferentiate into repair cells that are essential for axonal regeneration, and then redifferentiate into myelinating Schwann cells to restore nerve function. Although this remarkable plasticity has long been recognized, many questions remain unanswered regarding the signaling pathways regulating both myelination and the Schwann cell response to injury.