Node of Ranvier Spacing Along Single Axons is Prefigured by Clusters of Neuronal Neurofascin

The spacing of nodes of Ranvier crucially affects conduction properties along myelinated axons. It has been assumed that node position is primarily driven by the growth of myelin sheaths. Here, we show through longitudinal live imaging of node formation dynamics that stable clusters of the nodal cell adhesion molecule Neurofascin A accumulate at specific sites along axons prior to myelination. These sites are predictive of future node position as they can restrict extension of developing myelin sheaths. Animals that lack neuronal full-length Neurofascin A showed increased internodal distances and less regular spacing of nodes along single axons. Together, our data show that the axon can prefigure the position of its nodes of Ranvier and thus determine internodal spacing.