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The Journal of Neuroscience, September 1, 1999, 19(17):7278-7288
Formation of Compact Myelin Is Required for Maturation of the Axonal Cytoskeleton
Scott T. Brady1, Andrea S. Witt1, Laura L. Kirkpatrick2, Sylvie M. de Waegh3, Carol Readhead4, Pang-Hsien Tu5, and Virginia M.-Y. Lee5 1 University of Texas Southwestern Medical Center, Department of Cell Biology and Neuroscience, Dallas, Texas 75235-9039, 2 Baylor College of Medicine, Department of Molecular and Human Genetics, Houston, Texas 77030, 3 University of Wisconsin, Madison, Wisconsin 53706, 4 California Institute of Technology, Biological Imaging Center, Pasadena, California 91125, and 5 University of Pennsylvania School of Medicine, Pathology, and Laboratory Medicine, Philadelphia, Pennsylvania 19104-4283
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.
Key words: myelin; cytoskeleton; neurofilaments; oligodendrocytes; slow axonal transport; phosphorylation
Copyright © 1999 Society for Neuroscience 0270-6474/99/19177278-11$05.00/0
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