The canonical Wnt signaling pathway is not a promising therapeutic target for PNS regeneration enhancement

Abstract

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 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 Wnt signaling pathway is re-activated, suggesting that Wnt signaling plays an important role in PNS regeneration. To explore the potential of the Wnt pathway as a therapeutic target for enhancement of PNS recovery, we used a combination of genetic and pharmacological approaches to either activate or inhibit the Wnt signaling pathway during PNS recovery. We found that manipulating the Wnt signaling pathway does not alter PNS regeneration. Our data suggests that the Wnt signaling pathway is not a strong therapeutic target for the enhancement of PNS regeneration.