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

• Published in: The Journal of neuroscience Vol. 19; no. 17; pp. 7278 - 7288
• Main Authors: Brady, Scott T, Witt, Andrea S, Kirkpatrick, Laura L, de Waegh, Sylvie M, Readhead, Carol, Tu, Pang-Hsien, Lee, Virginia M.-Y
• Format: Journal Article
• Language: English
• Published: Legacy CDMS Soc Neuroscience 01.09.1999; Society for Neuroscience
• Subjects: Animals; Axonal Transport; Axons - physiology; Cytoskeleton - physiology; Life Sciences (General); Methionine - metabolism; Mice; Mice, Neurologic Mutants; Models, Neurological; Myelin Basic Protein - genetics; Myelin Basic Protein - metabolism; Myelin Sheath - physiology; Neurofilament Proteins - genetics; Neurofilament Proteins - metabolism; Neuroglia - physiology; Oligodendroglia - physiology; Optic Nerve - physiology; Polymerase Chain Reaction; Space life sciences; Visual Pathways - physiology; Non-Nasa Center; Nasa Discipline Neuroscience; NASA Discipline Neuroscience; Non-NASA Center
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.19-17-07278.1999

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.