Loss of intrinsic growth ability of mature CNS neurons is the main reason for the regeneration failure of CNS axons after injury. Previous studies have identified the PTEN/mTOR pathway and the JAK/STAT3 pathway as two important machineries regulating intrinsic regenerative ability. The two pathways worked synergistically to promote axon regeneration of RGCs after optic nerve injury. In this study, we co-deleted PTEN and mTOR in corticospinal motor neurons and the results didn’t reveal further enhance compared with PTEN single deletion. Using delayed PTEN deletion, our data suggested that intrinsic regenerative ability could be reversed in mature CSMNs. One-week delayed PTEN deletion promoted robust CST sprouting which suggested that the developmental decline of growth ability i...[ Read more ]

Loss of intrinsic growth ability of mature CNS neurons is the main reason for the regeneration failure of CNS axons after injury. Previous studies have identified the PTEN/mTOR pathway and the JAK/STAT3 pathway as two important machineries regulating intrinsic regenerative ability. The two pathways worked synergistically to promote axon regeneration of RGCs after optic nerve injury. In this study, we co-deleted PTEN and mTOR in corticospinal motor neurons and the results didn’t reveal further enhance compared with PTEN single deletion. Using delayed PTEN deletion, our data suggested that intrinsic regenerative ability could be reversed in mature CSMNs. One-week delayed PTEN deletion promoted robust CST sprouting which suggested that the developmental decline of growth ability is reversed in CSMNs. One-month delayed PTEN deletion after spinal cord injury stimulated CST axon regeneration beyond the lesion site suggested that injury-induced decrease of regeneration ability can also be reversed.