title: Anosmin-1 over-expression regulates oligodendrocyte precursor cell proliferation, migration and myelin sheath thickness.
abstract: During development of the central nervous system, anosmin-1 (A1) works as a chemotropic cue contributing to axonal outgrowth and collateralization, as well as modulating the migration of different cell types, fibroblast growth factor receptor 1 (FGFR1) being the main receptor involved in all these events. To further understand the role of A1 during development, we have analysed the over-expression of human A1 in a transgenic mouse line. Compared with control mice during development and in early adulthood, A1 over-expressing transgenic mice showed an enhanced oligodendrocyte precursor cell (OPC) proliferation and a higher number of OPCs in the subventricular zone and in the corpus callosum (CC). The migratory capacity of OPCs from the transgenic mice is increased in vitro due to a higher basal activation of ERK1/2 mediated through FGFR1 and they also produced more myelin basic protein (MBP). In vivo, the over-expression of A1 resulted in an elevated number of mature oligodendrocytes with higher levels of MBP mRNA and protein, as well as increased levels of activation of the ERK1/2 proteins, while electron microscopy revealed thicker myelin sheaths around the axons of the CC in adulthood. Also in the mature CC, the nodes of Ranvier were significantly longer and the conduction velocity of the nerve impulse in vivo was significantly increased in the CC of A1 over-expressing transgenic mice. Altogether, these data confirmed the involvement of A1 in oligodendrogliogenesis and its relevance for myelination.
authors: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca La Peraleda, s/n, 45071, Toledo, Spain.|Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Campus San Juan de Alicante, 03550, Alicante, Spain.
authors: Verónica
authors: V
authors: Murcia-Belmonte
authors: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca La Peraleda, s/n, 45071, Toledo, Spain.
authors: Pedro F
authors: PF
authors: Esteban
authors: Departamento de Ciencias Médicas, CRIB-Facultad de Medicina, Universidad de Castilla-La Mancha, C/Almansa 14, 02006, Albacete, Spain.
authors: José
authors: J
authors: Martínez-Hernández
authors: División de Neurociencias, Universidad Pablo de Olavide, Ctra. De Utrera, Km.1, 41013, Seville, Spain.
authors: Agnès
authors: A
authors: Gruart
authors: Departamento de Ciencias Médicas, CRIB-Facultad de Medicina, Universidad de Castilla-La Mancha, C/Almansa 14, 02006, Albacete, Spain.
authors: Rafael
authors: R
authors: Luján
authors: División de Neurociencias, Universidad Pablo de Olavide, Ctra. De Utrera, Km.1, 41013, Seville, Spain.
authors: José María
authors: JM
authors: Delgado-García
authors: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca La Peraleda, s/n, 45071, Toledo, Spain. fdec@sescam.jccm.es.
authors: Fernando
authors: F
authors: de Castro
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology* / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000196:embryology / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism / Q000502:physiology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism
chemical_list: C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496349:Fgfr1 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: Conduction velocity; Development; ERK1/2; Myelination; Oligodendrocyte; Proliferation; Subventricular zone