title: Cyclin D1 promotes neurogenesis in the developing spinal cord in a cell cycle-independent manner.
abstract: Neural stem and progenitor cells undergo an important transition from proliferation to differentiation in the G1 phase of the cell cycle. The mechanisms coordinating this transition are incompletely understood. Cyclin D proteins promote proliferation in G1 and typically are down-regulated before differentiation. Here we show that motoneuron progenitors in the embryonic spinal cord persistently express Cyclin D1 during the initial phase of differentiation, while down-regulating Cyclin D2. Loss-of-function and gain-of-function experiments indicate that Cyclin D1 (but not D2) promotes neurogenesis in vivo, a role that can be dissociated from its cell cycle function. Moreover, reexpression of Cyclin D1 can restore neurogenic capacity to D2-expressing glial-restricted progenitors. The neurogenic function of Cyclin D1 appears to be mediated, directly or indirectly, by Hes6, a proneurogenic basic helic-loop-helix transcription factor. These data identify a cell cycle-independent function for Cyclin D1 in promoting neuronal differentiation, along with a potential genetic pathway through which this function is exerted.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Agnès I
authors.initials: AI
authors.lastname: Lukaszewicz
authors.forename: David J
authors.initials: DJ
authors.lastname: Anderson
mesh_terms: D000818:Animals; D030161:Avian Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002642:Chick Embryo; D019938:Cyclin D1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D056742:Cyclin D2 / Q000235:genetics / Q000502:physiology; D004843:Epistasis, Genetic; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D019940:Genes, bcl-1; D051379:Mice; D009046:Motor Neurons / Q000166:cytology / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology / Q000637:transplantation; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology* / Q000502:physiology
chemical_list: D030161:Avian Proteins; D051792:Basic Helix-Loop-Helix Proteins; D019938:Cyclin D1; D056742:Cyclin D2; D034741:RNA, Small Interfering; C530105:Ccnd1 protein, mouse; C486196:Ccnd2 protein, mouse