title: Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system.
abstract: 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.
authors.affiliation: Université Pierre et Marie Curie, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), UMRS 975; Inserm U 975; CNRS, UMR 7225; Paris 75013, France.
authors.forename: Gabrièle
authors.initials: G
authors.lastname: Piaton
authors.forename: Marie-Stéphane
authors.initials: MS
authors.lastname: Aigrot
authors.forename: Anna
authors.initials: A
authors.lastname: Williams
authors.forename: Sarah
authors.initials: S
authors.lastname: Moyon
authors.forename: Vanja
authors.initials: V
authors.lastname: Tepavcevic
authors.forename: Imane
authors.initials: I
authors.lastname: Moutkine
authors.forename: Julien
authors.initials: J
authors.lastname: Gras
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Matho
authors.forename: Alain
authors.initials: A
authors.lastname: Schmitt
authors.forename: Heidi
authors.initials: H
authors.lastname: Soellner
authors.forename: Andrea B
authors.initials: AB
authors.lastname: Huber
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravassard
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
mesh_terms: D000818:Animals; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism*; D039961:Semaphorins / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D004676:Myelin Basic Protein; D039961:Semaphorins