text: Researchers prove that in the developing CNS, Nav1.2 is initially expressed at all forming nodes of Ranvier. Upon maturation, nodal Nav1.2 is down-regulated and replaced by Nav1.6.  Nav1.2 is also expressed during PNS node formation, which suggests that the switching of Nav-channel subtypes is a general phenomenon in the CNS and PNS.  In this same investigation, it was shown that Nav1.6 and Nav1.2 colocalize at many nodes of Ranvier during early myelination.  This also led to the suggestion that early clusters of Nav1.2 and Nav1.6 channels are destined to later become nodes of Ranvier. Neurofascin is also reported to be one of the first proteins to accumulate at newly forming nodes of Ranvier.  They are also found to provide the nucleation site for attachment of ankyrin G, Nav channels, and other proteins. The recent identification of the Schwann cell microvilli protein gliomedin as the likely binding partner of axonal neurofascin brings forward substantial evidence for the importance of this protein in recruiting Nav channels to the nodes of Ranvier.  Furthermore, Lambert et al. and Eshed et al. also indicates that neurofascin accumulates before Nav channels and is likely to have crucial roles in the earliest events associated with node of Ranvier formation.   Thus, multiple mechanisms may exist and work synergistically to facilitate clustering of Nav channels at nodes of Ranvier.