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VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.

ABSTRACT: Oligodendrocytes differentiate to wrap their plasma membranes around axons, forming the myelin sheath. A neuronal cue is one of the regulator elements controlling this process. Here, we demonstrate that VCAM1, which plays a key role throughout the immune system, is also expressed in oligodendrocytes, where it regulates the initiation of myelination. VCAM1 knockout mice exhibit reduced myelin thickness. Decreased myelin thickness is also observed in mutant mice of ?4 integrin, which is a neuronal VCAM1 ligand. Furthermore, CD69 is identified as one of the transcripts downregulated when VCAM1 is knocked down in oligodendrocytes. Knockdown of CD69 in mice indicates its role in myelination. Therefore, VCAM1 contributes not only to the initiation of myelination but also to its regulation through controlling the abundance of CD69, demonstrating that an intercellular molecule whose primary role is in the immune system can also play an unexpected role in the CNS.

SUBMITTER: Miyamoto Y

PROVIDER: S-EPMC5476804 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.

Miyamoto Yuki Y Torii Tomohiro T Tanoue Akito A Yamauchi Junji J

Nature communications 20161123

Oligodendrocytes differentiate to wrap their plasma membranes around axons, forming the myelin sheath. A neuronal cue is one of the regulator elements controlling this process. Here, we demonstrate that VCAM1, which plays a key role throughout the immune system, is also expressed in oligodendrocytes, where it regulates the initiation of myelination. VCAM1 knockout mice exhibit reduced myelin thickness. Decreased myelin thickness is also observed in mutant mice of α4 integrin, which is a neuronal ...[more]

PMID: 27876794

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Project description:Oligodendrocyte myelination depends on actin cytoskeleton rearrangement. Neural Wiskott-Aldrich syndrome protein(N-Wasp) is an actin nucleation factor that promotes polymerization of branched actin filaments. N-Wasp activity is essential for myelin membrane wrapping by Schwann cells, but its role in oligodendrocytes and CNS myelination remains unknown. Here we report that oligodendrocytes-specific deletion of N-Wasp in mice of both sexes resulted in hypomyelination (i.e., reduced number of myelinated axons and thinner myelin profiles), as well as substantial focal hypermyelination reflected by the formation of remarkably long myelin outfolds. These myelin outfolds surrounded unmyelinated axons, neuronal cell bodies, and other myelin profiles. The latter configuration resulted in pseudo-multimyelin profiles that were often associated with axonal detachment and degeneration throughout the CNS, including in the optic nerve, corpus callosum, and the spinal cord. Furthermore, developmental analysis revealed that myelin abnormalities were already observed during the onset of myelination, suggesting that they are formed by aberrant and misguided elongation of the oligodendrocyte inner lip membrane. Our results demonstrate that N-Wasp is required for the formation of normal myelin in the CNS. They also reveal that N-Wasp plays a distinct role in oligodendrocytes compared with Schwann cells, highlighting a difference in the regulation of actin dynamics during CNS and PNS myelination.SIGNIFICANCE STATEMENT Myelin is critical for the normal function of the nervous system by facilitating fast conduction of action potentials. During the process of myelination in the CNS, oligodendrocytes undergo extensive morphological changes that involve cellular process extension and retraction, axonal ensheathment, and myelin membrane wrapping. Here we present evidence that N-Wasp, a protein regulating actin filament assembly through Arp2/3 complex-dependent actin nucleation, plays a critical role in CNS myelination, and its absence leads to several myelin abnormalities. Our data provide an important step into the understanding of the molecular mechanisms underlying CNS myelination.

Dataset Information

VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.

Publications

VCAM1 acts in parallel with CD69 and is required for the initiation of oligodendrocyte myelination.

Similar Datasets

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