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

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 dep...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2018-10, Vol.25 (3), p.544-550.e3
Main Authors: Mayoral, Sonia R., Etxeberria, Ainhoa, Shen, Yun-An A., Chan, Jonah R.
Format: Article
Language:English
Subjects:
Animals
Axons - chemistry
Axons - physiology
Brain - cytology
Brain - physiology
Cell Differentiation
Cell Proliferation
Female
Male
Mice
Mice, Knockout
myelin
Myelin Sheath - physiology
Neurogenesis
neuron-glia interactions
oligodendrocyte
Oligodendroglia - cytology
Oligodendroglia - physiology
optic nerve
Optic Nerve - cytology
Optic Nerve - physiology
PTEN Phosphohydrolase - physiology
Signal Transduction
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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. [Display omitted] •Oligodendrocyte differentiation is not dependent on dynamic neuronal signals•Supra-threshold axon caliber is necessary for myelination in vivo•Dynamic neuronal signaling in not necessary for oligodendrocyte myelination•Neuronal signaling may be required for limiting myelin wraps 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.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.09.052