Receptor protein tyrosine phosphatase sigma (RPTPsigma) plays a role in inhibiting axon growth during development. It has also been shown to slow axon regeneration after peripheral nerve injury and inhibit axon regeneration in the optic nerve. Here, we assessed the ability of the corticospinal tract (CST) axons to regenerate after spinal hemisection and contusion injury in RPTPsigma deficient (RPTPsigma(-/-)) mice. We show that damaged CST fibers in RPTPsigma(-/-) mice regenerate and appear to extend for long distances after a dorsal hemisection or contusion injury of the thoracic spinal cord. In contrast, no long distance axon regeneration of CST fibers is seen after similar lesions in wild-type mice. In vitro experiments indicate that cerebellar granule neurons from RPTPsigma(-/-) mice have reduced sensitivity to the inhibitory effects of chondroitin sulfate proteoglycan (CSPG) substrate, but not myelin, which may contribute to the growth of CST axons across the CSPG-rich glial scar. Our data suggest that RPTPsigma may function to prevent axonal growth after injury in the adult mammalian spinal cord and could be a target for promoting long distance regeneration after spinal cord injury.
2009 Wiley-Liss, Inc.