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Open Access Green as soon as Postprint is submitted to ZB.
Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system.
Brain 134, 1156-1167 (2011)
Oligodendrocyte precursor cells, which persist in the adult central nervous system, are the main source of central nervous system remyelinating cells. In multiple sclerosis, some demyelinated plaques exhibit an oligodendroglial depopulation, raising the hypothesis of impaired oligodendrocyte precursor cell recruitment. Developmental studies identified semaphorins 3A and 3F as repulsive and attractive guidance cues for oligodendrocyte precursor cells, respectively. We previously reported their increased expression in experimental demyelination and in multiple sclerosis. Here, we show that adult oligodendrocyte precursor cells, like their embryonic counterparts, express class 3 semaphorin receptors, neuropilins and plexins and that neuropilin expression increases after demyelination. Using gain and loss of function experiments in an adult murine demyelination model, we demonstrate that semaphorin 3A impairs oligodendrocyte precursor cell recruitment to the demyelinated area. In contrast, semaphorin 3F overexpression accelerates not only oligodendrocyte precursor cell recruitment, but also remyelination rate. These data open new avenues to understand remyelination failure and promote repair in multiple sclerosis.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
semaphorin; oligodendrocyte precursor cell; recruitment; remyelination; gain and loss of function
ISSN (print) / ISBN
0006-8950
e-ISSN
1460-2156
Journal
Brain: A Journal of Neurology
Quellenangaben
Volume: 134,
Issue: 4,
Pages: 1156-1167
Publisher
Oxford University Press
Reviewing status
Peer reviewed
Institute(s)
Institute of Developmental Genetics (IDG)