Manipulation of Wnt Signaling Pathway during Peripheral Nerve Regeneration.

PNS injury initiates transcriptional changes in Schwann cells, satellite glial cells and PNS neurons that facilitate regeneration. The signaling pathways that control these transcriptional changes are not fully understood. The canonical/β-catenin Wnt signaling pathway is active during early stages of PNS development, where it controls radial axonal sorting and the onset of PNS myelination. Upon PNS injury, the canonical Wnt signaling pathway is re-activated, suggesting that canonical Wnt signaling plays an important role in PNS regeneration. To explore the potential of the canonical Wnt signaling pathway as a therapeutic target in enhancement of PNS recovery, we used a combination of genetic and pharmacological approaches to either activate or inhibit canonical Wnt signaling during PNS recovery. We found that manipulating canonical Wnt signaling does not alter PNS regeneration. Our data suggest that the canonical Wnt signaling pathway is not a strong therapeutic target for the enhancement of PNS regeneration.