Initiation of CNS Myelination in the Optic Nerve Is Dependent on Axon Caliber

Abstract

Summary: Emerging evidence suggests that neuronal signaling is important for oligodendrocyte myelination; however, the necessity of this signaling during development is unclear. By eliminating dynamic neuronal signaling along the developing optic nerve, we find that oligodendrocyte differentiation is not dependent on neuronal signaling and that the initiation of myelination is dependent on a permissive substrate, namely supra-threshold axon caliber. Furthermore, we show that loss of dynamic neuronal signaling results in hypermyelination of axons. We propose that oligodendrocyte differentiation is regulated by non-neuronal factors during optic nerve development, whereas myelination is sensitive to the biophysical properties of axonal diameter. : Mayoral et al. show that elimination of neuronal signaling via enucleation of the developing optic nerve of Wlds mice results in normal oligodendrocyte differentiation but disrupted myelination. Myelination is rescued when axons are enlarged prior to enucleation, showing that supra-threshold axon caliber, but not neuronal signaling, is necessary for myelination. Keywords: oligodendrocyte, myelin, neuron-glia interactions, optic nerve