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Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton

Brady, Scott T. and Witt, Andrea S. and Kirkpatrick, Laura L. and de Waegh, Sylvie M. and Readhead, Carol and Tu, Pang-Hsien and Lee, Virginia M.-Y. (1999) Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton. Journal of Neuroscience, 19 (17). pp. 7278-7288. ISSN 0270-6474. PMCID PMC6782532. doi:10.1523/jneurosci.19-17-07278.1999.

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Although traditional roles ascribed to myelinating glial cells are structural and supportive, the importance of compact myelin for proper functioning of the nervous system can be inferred from mutations in myelin proteins and neuropathologies associated with loss of myelin. Myelinating Schwann cells are known to affect local properties of peripheral axons (de Waegh et al., 1992), but little is known about effects of oligodendrocytes on CNS axons. The shiverer mutant mouse has a deletion in the myelin basic protein gene that eliminates compact myelin in the CNS. In shiverer mice, both local axonal features like phosphorylation of cytoskeletal proteins and neuronal perikaryon functions like cytoskeletal gene expression are altered. This leads to changes in the organization and composition of the axonal cytoskeleton in shiverer unmyelinated axons relative to age-matched wild-type myelinated fibers, although connectivity and patterns of neuronal activity are comparable. Remarkably, transgenic shiverer mice with thin myelin sheaths display an intermediate phenotype indicating that CNS neurons are sensitive to myelin sheath thickness. These results indicate that formation of a normal compact myelin sheath is required for normal maturation of the neuronal cytoskeleton in large CNS neurons.

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Additional Information:© 1999 Society for Neuroscience. Received Oct. 2, 1998; revised June 11, 1999; accepted June 11, 1999. This work was supported in part by National Institute of Neurological Disease and Stroke Grants NS23868 and NS23320 to S.T.B., a joint grant from NASA and the National Institute of Aging (NAG2–962/AG12646), the Welch Foundation (#1237), and the Muscular Dystrophy Association. We thank Milena Gould, Enid Romanelli, and Martha Stokely for technical support. C.R. acknowledges Cedars-Sinai Medical Center for its support.
Funding AgencyGrant Number
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
National Institute of AgingAG12646
Robert A. Welch Foundation1237
Muscular Dystrophy AssociationUNSPECIFIED
Subject Keywords:myelin; cytoskeleton; neurofilaments; oligodendrocytes; slow axonal transport; phosphorylation
Issue or Number:17
PubMed Central ID:PMC6782532
Record Number:CaltechAUTHORS:20191028-113959143
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Official Citation:Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton. Scott T. Brady, Andrea S. Witt, Laura L. Kirkpatrick, Sylvie M. de Waegh, Carol Readhead, Pang-Hsien Tu, Virginia M.-Y. Lee. Journal of Neuroscience 1 September 1999, 19 (17) 7278-7288; DOI: 10.1523/JNEUROSCI.19-17-07278.1999
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99488
Deposited By: Tony Diaz
Deposited On:28 Oct 2019 19:54
Last Modified:16 Nov 2021 17:47

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