Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system

Gabriele Piaton, Marie-Stephane Aigrot, Anna Williams, Sarah Moyon, Vanja Tepavcevic, Imane Moutkine, Julien Gras, Katherine S. Matho, Alain Schmitt, Heidi Soellner, Andrea B. Huber, Philippe Ravassard, Catherine Lubetzki

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)1156-1167
Number of pages12
JournalBrain
Volume134
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords / Materials (for Non-textual outputs)

  • semaphorin
  • oligodendrocyte precursor cell
  • recruitment
  • remyelination
  • gain and loss of function

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