Nodes of Ranvier are specialized axonal domains formed in response to a glial signal. Recent research advances have revealed that both CNS and PNS nodes form by several overlapping molecular mechanisms. However, the precise nature of these mechanisms and the hierarchy existing between them is considerably different in CNS versus PNS nodes. Namely, the Schwann cells of the PNS, which directly contact the nodal axolemma, secrete proteins that cluster axonodal components at the edges of the growing myelin segment. In contrast, the formation of CNS nodes, which are not contacted by the myelinating glia, is surprisingly similar to the assembly of the axon initial segment and depends largely on axonal diffusion barriers.
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