Induction of neuropilins-1 and -2 and their ligands, Sema3A, Sema3F, and VEGF, during Wallerian degeneration in the peripheral nervous system

The neuropilins, NP-1 and NP-2, are coreceptors for Sema3A and Sema3F, respectively, both of which are repulsive axonal guidance molecules. NP-1 and NP-2 are also coreceptors for vascular endothelial growth factor (VEGF). The neuropilins and their ligands are known to play prominent roles in axonal pathfinding, fasciculation, and blood vessel formation during peripheral nervous system (PNS) development. We confirmed a prior report (Exp. Neurol. 172 (2001) 398) that VEGF mRNA levels rise during Wallerian degeneration in the PNS and herein demonstrate that NP-1, NP-2, Sema3A, and Sema3F mRNA levels increase in peripheral nerves distal to a transection or crush injury. In a sciatic nerve crush model, in which axonal regeneration is robust, the highest levels of Sema3F mRNA below the injury site are in the epi- and perineurium. Our results suggest the possibility that the neuropilins and their semaphorin ligands serve to guide, rather than to impede, regenerating axons in the adult PNS.