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Cyclin D1 promotes neurogenesis in the developing spinal cord in a cell cycle-independent manner

Lukaszewicz, Agnès I. and Anderson, David J. (2011) Cyclin D1 promotes neurogenesis in the developing spinal cord in a cell cycle-independent manner. Proceedings of the National Academy of Sciences of the United States of America, 108 (28). pp. 11632-11637. ISSN 0027-8424. PMCID PMC3136279. doi:10.1073/pnas.1106230108.

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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-offunction 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.

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Anderson, David J.0000-0001-6175-3872
Additional Information:© 2011 National Academy of Sciences. Contributed by David J. Anderson, May 25, 2011 (sent for review February 14, 2011). Published online before print June 27, 2011. We thank D. Perez and R. Diamond for assistance with the FACS experiments; S. Pease, B. Kennedy, J. Alex, L.C. Sandoval, and the staff of the Transgenic Animal Facility at California Institute of Technology for assistance with mouse breeding and care; M. Martinez for genotyping mouse lines; R. Ho for technical assistance; G. Mosconi for laboratory management; and G. Mancuso for administrative assistance. We thank Dr. F. Pituello (Université Toulouse III) for sharing the chick cD1 and cD2 cDNA; Dr. D. Henrique (Faculdade de Medicina de Lisboa) for sharing the cHes5-1, cHes5-2, cHes5-3, and cHes6-2 in situ hybridization probes and cHes5-2 and cHes6-2 cDNA; and Dr. D. Rowitch (University of California, San Francisco) for sharing his NeuroM antibody. AMV, Engrail-1, and QCPN hybridomas were obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development and maintained by the Department of Biological Sciences, University of Iowa. This work was supported by funding from Fondation Cino del Duca, Amyotrophic Lateral Sclerosis Association, the Howard Hughes Medical Institute, the Pritzker Neurogenesis Consortium, the California Institute for Regenerative Medicine postdoctoral training fellowship, and the National Institutes of Health (Grant RO1-NS23476). D.J.A. is an investigator for the Howard Hughes Medical Institute. Author contributions: A.I.L. and D.J.A. designed research, A.I.L. performed research, and A.I.L. and D.J.A. wrote the paper.
Funding AgencyGrant Number
Fondation Cino del DucaUNSPECIFIED
Amyotrophic Lateral Sclerosis AssociationUNSPECIFIED
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Pritzker Neurogenesis ConsortiumUNSPECIFIED
California Institute for Regenerative Medicine (CIRM)UNSPECIFIED
Subject Keywords:neuronal specification; developmental switch; Notch signaling
Issue or Number:28
PubMed Central ID:PMC3136279
Record Number:CaltechAUTHORS:20110725-095339268
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:24523
Deposited On:25 Jul 2011 18:00
Last Modified:09 Nov 2021 16:24

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