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2002 Fiscal Year Final Research Report Summary

Roles of cell cycle regulatory protein p27 in murine neocortical histogenesis

Research Project

Project/Area Number 13670837
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionKeio University

Principal Investigator

TAKAHASHI Takao  Keio University, School of Medicine, Professor, 医学部, 教授 (80171495)

Co-Investigator(Kenkyū-buntansha) MITSUHASHI Takayuki  Keio University, School of Medicine, Instructor, 医学部, 助手 (80338110)
Project Period (FY) 2001 – 2002
Keywordscerebral histogenesis / cell cycle / development / mouse / neuronal progenitor / CDK
Research Abstract

p27^<kip1> is a cell cycle regulatory protein that inhibits G1 phase progression and induces cell differentiation. In p27^<kip1> knockout mouse (p27KO), the size of the brain is increased by about 30 %. We previously observed that both thickness and number of non-GABAergic neurons in the cortical layers II-IV were significantly increased in p27KO as compared to the WT littermates. These suggest that output from the NPCs in the middle to late period of neuronogenesis was increased by loss of function of p27^<kip1>. To investigate the histogenetic mechanisms of the cortical malformation in p27KO, we have studied proliferation and differentiation characteristics of the NPCs in the p27KO at embryonic day 14 (E14).
The cell cycle length of the NPCs at E14 was indistinguishable between p27KO and WT. However, the number of the newly differentiated neurons (Q cells) at E14 was reduced in p27KO. The consequence is that there is proliferative augmentation of NPCs in the p27KO animals at E14. The distribution pattern of the Q cells in the p27KO was also abnormal. The exit behavior of Q cells from the proliferative epithelium is bimodal in both genotypes ; partitioned into rapidly and slowly exiting subpopulations. The reduction in the Q fraction in the p27KO is assignable entirely to the rapidly exiting subset of Q cells.
The neocortical malformation in the p27KO is likely to be attributable to an abnormal pattern of the ascent of Q fraction during the middle phase of neuronogenetic interval.

  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Miyama S: "Continuity with ganglionic eminence modulates interkinetic nuclear migration in the neocortical pseudostratified ventricular epithelium"Exp Neurol. 169. 486-495 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mitsuhashi T: "Overexpression of p27Kip1 lengthens G1-phase in a mouse model that targets inducible gene expression to CNS progenitor cells"Proc Natl Acad Sci USA. 98. 6435-6440 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三橋 隆行: "神経系前駆細胞の分裂動態と大脳皮質発生"医学のあゆみ. 201. 754-758 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 三橋 隆行: "大脳皮質発生の数学モデル"Brain Medical. 14. 28-32 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Goto T: "Developmental regulation of the effects of fibroblast growth factor-2 and 1-octanol on neuronogenesis : implications for a hypothesis relating to mitogen-antimitogen"J Neurosci Res. 69. 714-722 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Cai L: "Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior"J Neurosci Res. 69. 731-744 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi T: "Analysis of cell generation in the telencephalic neuroepithelium"Methods Mol Biol. 198. 101-113 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nowalowski RS: "Population dynamics during cell proliferation and neuronogenesis in the developing murine neocortex"Results Probl Cell Differ.. 39. 1-25 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Caviness, VS Jr.: "Development of the Neocortex"Eds. A. Goffinet and P. Rakic. Springer Verlag, Berlin. 107-143 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi T: "Handbook of Developmental Cognitive Neuroscience"Eds. Nelson CA, Luciana M. The MIT Press, Cambridge. 3-22 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi T: "Analysis of cell generation in the telencephalic neuroepithelium. In : Neural Stem Cells : Methods and Protocols"Eds. Zigova T, Sanberg PR and Sanchez-Ramos. The MIT Press, Cambridge. (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Caviness, VS: "Neocortical neuronogenesis : the G1 restriction point as master integrative mechanism. In : The Newborn Brain-Scientific Basis and Clinical Applications"Eds. Lagercrantz H and Hanson M. Cambridge University Press, Cambridge. 46-66 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Caviness VS: "Neurscience Frontiers Tsukuba"Ed. Ezaki L. Universal Academy Press, Inc, Tokyo. (In press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Caviness VS: "Morphogenesis of the human cerebral cortex. In : Disorders of neural migration"Ed. Barth P. Cambridge University Press, Cambridge. 1-23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyama S, Takahashi T, Goto T, Bhide PG, Caviness VS Jr.: "Continuity with ganglionic eminence modulates interkinetic nuclear migration in the neocortical pseudostratified ventricular epithelium"Exp Neurol. 169-2. 486-495 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsuhashi T, Aoki Y, Eksioglu YZ, Takahashi T, Bhide PG, Reeves SA, Caviness VS Jr.: "Overexpression of p27Klp1 lengthens G1-phase in a mouse model that targets inducible gene expression to CNS progenitor cells"Proc Natl Acad Sci USA. 98-11. 6435-6440 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsuhashi T, Takahashi T.: "Cell cycle regulation of neural progenitor cells and neocortical histogenesis (In Japanese)"Igaku-no-ayumi. 201. 754-758 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsuhashi T, Takahashi T.: "Mathematical model for cerebral cortical histogenesis (In Japanese)"Brain Medical. 14. 28-32 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Goto T, Takahashi T, Miyama S, Nowakowski RS, Bhide PG, Caviness VS Jr.: "Developmental regulation of the effects of fibroblast growth factor-2 and 1-octanol on neuronogenesis : implications for a hypothesis relating to mitogen-antimitogen opposition"J Neurosci Res. 69-6. 714-722 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Cai L, Hayes NL, Takahashi T, Caviness VS Jr, Nowakowski RS.: "Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior"J Neurosci Res. 69-6. 731-744 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T, Caviness VS Jr, Bhide PG.: "Analysis of cell generation in the telencephalic neuroepithelium"Methods Mol Biol. 101-113 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nowakowski RS, Caviness VS Jr, Takahashi T, Hayes NL.: "Population dynamics during cell proliferation and neuronogenesis in the developing murine neocortex"Results Probl Cell Differ. 1-25 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Caviness,VS Jr., T.Takahashi, Nowakowski,RS, eds.A.Goffinet and P.I: "Neuronogenesis and the early events of neocortical histogenesis, Development of the Neocortex"Springer Verlag. 107-143 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T, Caviness VS Jr, Nowakowski RS, Eds.Nelson CA, Luciana M.: "Neocortical neuronogenesis : regulation, control points and a strategy of structural variation, Handbook of Developmental Cognitive Neuroscience"The MIT Press. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T, Caviness VS, Bhide PG, Eds, Zigo Sanberg PR and Sanchez-Ramos: "Analysis of cell generation in the telencephalic neuroepithelium, Neural Stem Cells : Methods and Protocols"The MIT Press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Caviness,VS, Takahashi T, Nowakowski RS, Eds.Lagercrantz H and Hanson M: "Neocortical neuronogenesis : the G1 restriction point as master integrative mechanism, The Newborn Brain - Scientific Basis and Clinical Applica"Cambridge Univ Press.. 46-66 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Caviness VS, Ed.Barth P.: "Morphogenesis of the human cerebral cortex, Disorders of neural migration"Cambridge University Press. 1-23 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Caviness VS, Takahashi T, Nowakowski RS, Ed. Ezaki L.: "Neocortical neuronogenesis : regulation, control points and a strategy of structural variation, Neurscience Frontiers Tsukuba"Universal Academy Press, Inc (in press).

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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