Genetic mutation of the semaphorin 3A receptor component neuropilin-1 in neurons does not enhance corticospinal tract regeneration

After a spinal cord lesion, a myriad of axon growth inhibitors present in myelin and in the neural scar contribute to the failure of injured axons to regenerate. Class 3 semaphorins are repulsive axon guidance cues that are induced in the meningeal fibroblasts that infiltrate the neural scar. Most if not all injured spinal cord neurons, including neurons that form the corticospinal tract (CST), continue to express the semaphorin receptor components neuropilin (Npn-1 and 2) and plexinAs. This had led to the hypothesis that semaphorin/neuropilin signalling limits axonal regeneration through the scar. To test this hypothesis we have investigated the regeneration of the CST in mice with an Npn-1-deletion specifically targeted to neurons and in littermate control mice. Mice deficient in Npn-1 in neurons do not exhibit enhanced regenerative growth of injured CST axons and do not display improved recovery of motor function as compared to control littermates. We therefore conclude that Npn-1/Sema3A signalling does not have a major impact on the failure of injured CST axons to regenerate. This illustrates that neuron-specific targeting of a single ligand-receptor pair (Sema3A/Npn-1) in the multi-component, divergent semaphorin/neuropilin/ plexin signalling pathway is insufficient to enhance regeneration of the CST.