Dataset Information

Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve.

ABSTRACT: Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes both in vitro and in an animal model of multiple sclerosis, but the possible role of LIF signaling in myelination during normal development has not been investigated. We find that LIF(-/-) mice have a pronounced myelination defect in optic nerve at postnatal day 10. Myelin basic protein (MBP)- and proteolipid protein (PLP)-positive myelin was evident throughout the optic nerve in the wild-type mice, but staining was present only at the chiasmal region in LIF(-/-) mice of the same age. Further experiments suggest that the myelination defect was a consequence of a delay in maturation of oligodendrocyte precursor cell (OPC) population. The number of Olig2-positive cells was dramatically decreased in optic nerve of LIF(-/-) mice, and the distribution of Olig2-positive cells was restricted to the chiasmal region of the nerve in a steep gradient toward the retina. Gene expression profiling and cell culture experiments revealed that OPCs from P10 optic nerve of LIF(-/-) mice remained in a highly proliferative immature stage compared with littermate controls. Interestingly, by postnatal day 14, MBP immunostaining in the LIF(-/-) optic nerve was comparable to that of LIF(+/+) mice. These results suggest that, during normal development of mouse optic nerve, there is a defined developmental time window when LIF is required for correct myelination. Myelination seems to recover by postnatal day 14, so LIF is not necessary for the completion of myelination during postnatal development.

SUBMITTER: Ishibashi T

PROVIDER: S-EPMC2782399 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve.

Ishibashi Tomoko T Lee Philip R PR Baba Hiroko H Fields R Douglas RD

Journal of neuroscience research 20091101 15

Leukemia inhibitory factor (LIF) promotes the survival of oligodendrocytes both in vitro and in an animal model of multiple sclerosis, but the possible role of LIF signaling in myelination during normal development has not been investigated. We find that LIF(-/-) mice have a pronounced myelination defect in optic nerve at postnatal day 10. Myelin basic protein (MBP)- and proteolipid protein (PLP)-positive myelin was evident throughout the optic nerve in the wild-type mice, but staining was prese ...[more]

PMID: 19598242

Similar Datasets

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

Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve.

Publications

Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets