title: The transmembrane semaphorin Sema4D/CD100, an inhibitor of axonal growth, is expressed on oligodendrocytes and upregulated after CNS lesion.
abstract: Semaphorins are a family of secreted and membrane-bound proteins, known to regulate axonal pathfinding. Sema4D, also called CD100, was first isolated in the immune system where it is involved in B and T cell activation. We found that in the mouse, Sema4D is expressed in cells throughout the CNS white matter, with a peak during the myelination period. Double-labeling experiments with different markers of oligodendrocyte lineage such as olig1, olig2, platelet-derived growth factor receptor alpha, and proteolipid protein showed that Sema4D was expressed selectively by oligodendrocytes and myelin. The presence of Sema4D in myelin was confirmed using Western blot. Sema4D expression in myelinating oligodendrocytes was further observed using neuron-oligodendrocyte cocultures. Moreover, using stripe assay, we found that Sema4D is strongly inhibitory for postnatal sensory and cerebellar granule cell axons. This prompted us to examine whether Sema4D expression is modified after CNS injury. At 8 d after spinal cord lesions, Sema4D expression was strongly upregulated in oligodendrocytes at the periphery of the lesion. Sema4D-positive cells were not colabeled with the astrocyte marker GFAP, with the microglial and macrophagic marker isolectin B4, or with NG2, a marker of oligodendrocyte precursors. This upregulation was transient because from 1 month after the lesion, Sema4D expression was back to its normal level. These results indicate that Sema4D is a novel inhibitory factor for axonal regeneration expressed in myelin.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U106, Hôpital de la Salpêtrière, 75013 Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moreau-Fauvarque
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kumanogoh
authors.forename: Emeline
authors.initials: E
authors.lastname: Camand
authors.forename: Céline
authors.initials: C
authors.lastname: Jaillard
authors.forename: Gilles
authors.initials: G
authors.lastname: Barbin
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boquet
authors.forename: Christopher
authors.initials: C
authors.lastname: Love
authors.forename: E Yvonne
authors.initials: EY
authors.lastname: Jones
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kikutani
authors.forename: Catherine
authors.initials: C
authors.lastname: Lubetzki
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dusart
authors.forename: Alain
authors.initials: A
authors.lastname: Chédotal
mesh_terms: D000818:Animals; D015703:Antigens, CD; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D039961:Semaphorins; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C093224:CD100 antigen; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D039961:Semaphorins