Neurite outgrowth inhibitor Nogo-A establishes spatial segregation and extent of oligodendrocyte myelination
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A requisite component of nervous system development is the achievement of cellular recognition and spatial segregation through competition-based refinement mechanisms. Competition for available axon space by myelinating oligodendrocytes ensures that all relevant CNS axons are myelinated properly. To ascertain the nature of this competition, we generated a transgenic mouse with sparsely labeled oligodendrocytes and establish that individual oligodendrocytes occupying similar axon tracts can greatly vary the number and lengths of their myelin internodes. Here we show that intercellular interactions between competing oligodendroglia influence the number and length of myelin internodes, referred to as myelinogenic potential, and identify the amino-terminal region of Nogo-A, expressed by oligodendroglia, as necessary and sufficient to inhibit this process. Exuberant and expansive myelination/remyelination is detected in the absence of Nogo during development and after demyelination, suggesting that spatial segregation and myelin extent is limited by microenvironmental inhibition. We demonstrate a unique physiological role for Nogo-A in the precise myelination of the developing CNS. Maximizing the myelinogenic potential of oligodendrocytes may offer an effective strategy for repair in future therapies for demyelination.
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Internode length and the number of internodes elaborated per OL vary greatly between CNS regions.
“Internode length and the number of internodes elaborated per OL vary greatly between CNS regions (Butt et al., 1994; Murtie et al., 2007; Chong et al., 2012)”
From Oligodendrocyte Dynamics in the Healthy Adult CNS: Evidence for Myelin Remodeling (2013) · cites this paper as Chong et al., 2012
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- Authors
- Chong, S. Y. C., Rosenberg, S. S., Fancy, S. P. J., Zhao, C., Shen, Y.-A. A., Hahn, A. T., McGee, A. W., Xu, X., Zheng, B., Zhang, L. I., Rowitch, D. H., Franklin, R. J. M., Lu, Q. R., & Chan, J. R.
- Affiliations
- University of Southern California (US)
- Broad Institute (US)
- University of Cambridge (GB)
- University of California, San Francisco (US)
- The University of Texas Southwestern Medical Center (US)
- University of California San Diego (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-12-12
- Volume
- 109
- Issue
- 4
- Pages
- 1299-1304
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3268264
- OpenAlex
- W2056928450
- Cited by
- 232
- References
- 33
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 8 · 2023: 17 · 2022: 11 · 2021: 20 · 2020: 18 · 2019: 17 · 2018: 16 · 2017: 25 · 2016: 14 · 2015: 17 · 2014: 21 · 2013: 16 · 2012: 5
- FWCI
- 4.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (079249)
- National Institute of Neurological Disorders and Stroke (R01NS054734, R01NS062796, NS062796-02)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- Nogo-A, oligodendrocyte myelination, demyelination, remyelination, central nervous system development, transgenic mice
- MeSH terms
- Nogo Proteins, Animals, Central Nervous System, Demyelinating Diseases, Histological Techniques, Mice, Transgenic, Microscopy, Electron, Microspheres, Myelin Proteins, Myelin Sheath, Oligodendroglia, Polystyrenes, Ultracentrifugation, Blotting, Western, RNA, Small Interfering, Mice, Gene Knockdown Techniques
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