Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Mayoral SR

PROVIDER: S-EPMC6258034 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Mayoral Sonia R SR Etxeberria Ainhoa A Shen Yun-An A YA Chan Jonah R JR

Cell reports 20181001 3

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 sign ...[more]

PMID: 30332636

Similar Datasets

Project description:In this study, we identify genomic regions that modulate the number of necrotic axons in optic nerves of a family of mice, some of which have severe glaucoma, and define a set of high priority positional candidate genes that modulate retinal ganglion cell (RGC) axonal degeneration. A large cohort of the BXD family were aged to greater than 13 months of age. Optic nerves from 74 strains and the DBA/2J (D2) parent were harvested, sectioned, and stained with p-phenylenediamine. Numbers of necrotic axons per optic nerve cross-section were counted from 1 to 10 replicates per genotype. Strain means and standard errors were uploaded into GeneNetwork 2 for mapping and systems genetics analyses (Trait 18614). The number of necrotic axons per nerve ranged from only a few hundred to more than 4,000. Using conventional interval mapping as well as linear mixed model mapping, we identified a single locus on chromosome 12 between 109 and 112.5 Mb with a likelihood ratio statistic (LRS) of ~18.5 (p genome-wide ~0.1). Axon necrosis is not linked to locations of major known glaucoma genes in this family, including Gpnmb, Tyrp1, Cdh11, Pou6f2, and Cacna2d1. This indicates that although these genes contribute to pigmentary dispersion or elevated IOP, none directly modulates axon necrosis. Of 156 positional candidates, eight genes-CDC42 binding protein kinase beta (Cdc42bpb); eukaryotic translation initiation factor 5 (Eif5); BCL2-associated athanogene 5 (Bag5); apoptogenic 1, mitochondrial (Apopt1); kinesin light chain 1 (Klc1); X-ray repair cross complementing 3 (Xrcc3); protein phosphatase 1, regulatory subunit 13B (Ppp1r13b); and transmembrane protein 179 (Tmem179)-passed stringent criteria and are high priority candidates. Several candidates are linked to mitochondria and/or axons, strengthening their plausible role as modulators of ON necrosis. Additional studies are required to validate and/or eliminate plausible candidates. Surprisingly, IOP and ON necrosis are inversely correlated across the BXD family in mice >13 months of age and these two traits share few genes among their top ocular and retinal correlates. These data suggest that the two traits are independently modulated or that a more complex and multifaceted approach is required to reveal their association.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets