title: Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system.
abstract: The specific functions of intrinsic regulators of oligodendrocyte progenitor cell (OPC) division are poorly understood. Type 2 cyclin-dependent kinase (Cdk2) controls cell cycle progression of OPCs, but whether it acts during myelination and repair of demyelinating lesions remains unexplored. Here, we took advantage of a viable Cdk2(-/-) mutant mouse to investigate the function of this cell cycle regulator in OPC proliferation and differentiation in normal and pathological conditions. During central nervous system (CNS) development, Cdk2 loss does not affect OPC cell cycle, oligodendrocyte cell numbers, or myelination. However, in response to CNS demyelination, it clearly alters adult OPC renewal, cell cycle exit, and differentiation. Importantly, Cdk2 loss accelerates CNS remyelination of demyelinated axons. Thus, Cdk2 is dispensable for myelination but is important for adult OPC renewal, and could be one of the underlying mechanisms that drive adult progenitors to differentiate and thus regenerate myelin.
authors.affiliation: UMR-S975, Centre de Recherche de l'Institut du Cerveau et de la Moelle Epinière, Université Pierre et Marie Curie-Paris 6, Paris 75013, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Caillava
authors.forename: Renaud
authors.initials: R
authors.lastname: Vandenbosch
authors.forename: Beata
authors.initials: B
authors.lastname: Jablonska
authors.forename: Cyrille
authors.initials: C
authors.lastname: Deboux
authors.forename: Giulia
authors.initials: G
authors.lastname: Spigoni
authors.forename: Vittorio
authors.initials: V
authors.lastname: Gallo
authors.forename: Brigitte
authors.initials: B
authors.lastname: Malgrange
authors.forename: Anne
authors.initials: A
authors.lastname: Baron-Van Evercooren
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D002490:Central Nervous System / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics*; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009416:Nerve Regeneration / Q000502:physiology; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics*; D009836:Oligodendroglia / Q000378:metabolism
chemical_list: C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2