Schwann cell plasticity after spinal cord injury shown by neural crest lineage tracing

After spinal cord injury (SCI), various cell types are recruited to the lesion site, including Schwann cells, which originate in the neural crest and normally myelinate axons in the peripheral nervous system. Here, we investigated the differentiation states, migration patterns, and roles of neural crest derivatives following SCI, using two transgenic mouse lines carrying neural crest-specific reporters, P0-Cre/Floxed-EGFP and Wnt1-Cre/Floxed-EGFP. In these mice, EGFP is expressed only in the neural crest cell lineage. Immunohistochemical analysis revealed that most of the EGFP(+) cells that infiltrated the lesion site after SCI were Schwann cells. Seven days after SCI, the P0-positive, mature Schwann cells residing at the nerve roots had dedifferentiated into P0(-)/p75(+) immature Schwann cells, which proliferated and began migrating into the lesion site. The dedifferentiation of the Schwann cells was corroborated by their expression of phosphorylated c-Jun, which promotes dedifferentiation and inhibits the expression of myelin-associated genes in the peripheral nerves. Thereafter, the number of EGFP(+)/p75(+) immature Schwann cells decreased and that of EGFP(+)/P0(+) mature cells increased gradually, indicating that the cells redifferentiated into mature Schwann cells within the lesion site. This study draws on the advantages offered by transgenic mouse lines bearing a genetic cell-lineage marker and extends previous work by describing the origins and behavior of the neural crest-derived cells that contribute to endogenous repair after SCI. This process, involving Schwann cell plasticity, is a novel repair mechanism for the lesioned mammalian spinal cord.