Neuropilin and class 3 semaphorins in nervous system regeneration

TY - JOUR

T1 - Neuropilin and class 3 semaphorins in nervous system regeneration

AU - De Winter, Fred

AU - Holtmaat, Anthony J D G

AU - Verhaagen, J.

PY - 2002

Y1 - 2002

N2 - Injury to the mature mammalian central nervous system (CNS) is often accompanied by permanent loss of function of the damaged neural circuits. The failure of injured CNS axons to regenerate is thought to be caused, in part, by neurite outgrowth inhibitory factors expressed in and around the lesion. These include several myelin associated inhibitors, proteoglycans, and tenascin-R. Recent studies have documented the presence of class 3 semaphorins in fibroblast-like meningeal cells present in the core of the neural scar formed following CNS injury. Class 3 semaphorins display neurite growth-inhibitory effects on growing axons during embryonic development. The induction of the expression of class 3 semaphorins in the neural scar and the persistent expression of their receptors, the neuropilins and plexins, by injured CNS neurons suggest that they contribute to the regenerative failure of CNS neurons. Neuropilins are also expressed in the neural scar in a subpopulation of meningeal fibroblast and in neurons in the vicinity of the scar. Semaphorin/neuropilin signaling might therefore also be important for cell migration, angiogenis and neuronal cell death in or around neural scars. In contrast to neurons in the CNS, neuropilin/plexin positive neurons in the PNS do display long distance regeneration following injury. Injured PNS neurons do not encounter a semaphorin positive neural scar. Furthermore, Semaphorin 3A is downregulated in the regenerating spinal motor neurons themselves. This was accompanied by a transient upregulation of Semaphorin 3A in the target muscle. These observations suggest that the injury induced regulation of Semaphorin 3A in the PNS contributes to successful regeneration and target reinnervation. Future studies in genetically modified mice should provide more insight into the mechanisms by which neuropilins and semaphorins influence nervous system regeneration and degeneration.

AB - Injury to the mature mammalian central nervous system (CNS) is often accompanied by permanent loss of function of the damaged neural circuits. The failure of injured CNS axons to regenerate is thought to be caused, in part, by neurite outgrowth inhibitory factors expressed in and around the lesion. These include several myelin associated inhibitors, proteoglycans, and tenascin-R. Recent studies have documented the presence of class 3 semaphorins in fibroblast-like meningeal cells present in the core of the neural scar formed following CNS injury. Class 3 semaphorins display neurite growth-inhibitory effects on growing axons during embryonic development. The induction of the expression of class 3 semaphorins in the neural scar and the persistent expression of their receptors, the neuropilins and plexins, by injured CNS neurons suggest that they contribute to the regenerative failure of CNS neurons. Neuropilins are also expressed in the neural scar in a subpopulation of meningeal fibroblast and in neurons in the vicinity of the scar. Semaphorin/neuropilin signaling might therefore also be important for cell migration, angiogenis and neuronal cell death in or around neural scars. In contrast to neurons in the CNS, neuropilin/plexin positive neurons in the PNS do display long distance regeneration following injury. Injured PNS neurons do not encounter a semaphorin positive neural scar. Furthermore, Semaphorin 3A is downregulated in the regenerating spinal motor neurons themselves. This was accompanied by a transient upregulation of Semaphorin 3A in the target muscle. These observations suggest that the injury induced regulation of Semaphorin 3A in the PNS contributes to successful regeneration and target reinnervation. Future studies in genetically modified mice should provide more insight into the mechanisms by which neuropilins and semaphorins influence nervous system regeneration and degeneration.

KW - Animals

KW - Cell Death

KW - Cell Movement

KW - Humans

KW - Ligands

KW - Neovascularization, Pathologic

KW - Nerve Regeneration

KW - Neuropilins

KW - Olfactory Pathways

KW - Peripheral Nervous System

KW - Semaphorins

KW - Status Epilepticus

KW - Journal Article

KW - Review

M3 - Article

C2 - 12613548

SN - 0065-2598

VL - 515

SP - 115

EP - 139

JO - Advances in Experimental Medicine and Biology

JF - Advances in Experimental Medicine and Biology

ER -