Neurite outgrowth inhibitors at the node of Ranvier

Du-Yu Nie; Qi-Dong Hu; Quan-Hong Ma; Melitta Schachner; Zhi-Cheng Xiao

Abstract：Nodes of Ranvier and paranodes are polarized-domains along myelinated axons. Increasing evidence indicate that glia-derived neurite outgrowth inhibitory molecules which suppress axonal regeneration following injury in the central nervous system (CNS), such as tenascins, chondroitin sulphate proteoglycans, MAG, Nogo and OMgp, are specifically accumulated at the regions of nodes of Ranvier. These molecules show potent inhibition of neurite outgrowth in tissue culture. In some null mutation animals, axonal sprouting was observed at the node, suggesting that these inhibitory molecules may physiologically ensure the integrity of axons and prevent random and erroneous connection between axons. However, most null mutation animal models have so far revealed no significant improvement in CNS regeneration. Are these so-called inhibitors really the culprits in the failure of regeneration? The disparities between the in vitro and in vivo behaviours of these "inhibitors" and their specific locations have led us to reassess other physiological roles and functions. Given the bi-directional properties of axo-glial interaction, in this review, we propose that not only do the inhibitory molecules signal to neuronal receptors to regulate axonal polarization, ion channel function and axonal branching, but also axonal molecules can signal back to oligodendrocytes via glia receptors to mediate oligodendroglial development at the regions of nodes of Ranview.