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2000 Fiscal Year Final Research Report Summary

ROLES OF FIBROBLAST GROWTH FACTOR (B-FGF) AND GAP JUNCTION ON NEOCORTICAL HISTOGENESIS

Research Project

Project/Area Number 11670784
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, SCOOL OF MEDICINE, Dept.of PEDIATRICS ASSOCIATE PROFESSOR, 医学部, 助教授 (80171495)

Project Period (FY) 1999 – 2000
KeywordsCerebral Histogenesis / Mouse / Cell Cycle / Tissue Culture / Gap Junction / Basic Fibroblast Growth Factor / Octanol
Research Abstract

We have examined the cell cycle progression in explants cultured with FGF-2 or 1-octanol. FGF-2 is representative of physiologic mitogens respecting the neocortical PVE.1-octanol, on the other hand, has been demonstrated to mediate a countering antimitogenic effect through gap junction blockade.
In vivo, there are two options for postmitotic cells, either to exit the cycle and migrate out of the VZ (fate to Q fraction) or to re-enter S phase and continue to cycle (fate to P fraction). In the explants, by contrast, a substantial proportion makes neither of these choices but instead persists in the VZ in an indeterminate state (I fraction). The phenomenon is modulated, in opposing directions and to different degree, by FGF-2 and 1-octanol. Modulation by these mitogenic and antimitogenic agents is observed only in the more advanced region of the neurogenetic gradient. The phenomenon is a relatively selective one in that the majority of other vital properties of the epithelium are little altered : the epithelium maintains its architectonic integrity and there is no interruption of interkinetic nuclear migration, respecting cell cycle phases. Moreover, there is no augmentation in the generally low occurrence rate of pyknosis. That is, these conditions of culture appear to have unmasked relatively selectively mechanisms regulatory to the proliferative fates of cells of the PVE.Importantly, mechanisms by which this effect is modulated by FGF-2 or 1-octanol are evidently developmentally regulated, expressed only in the relatively advanced region of the neurogenetic gradient.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Mitsuhashi,T: "Overexpression of p27Kip1 lengthens G1-phase in a mouse model that targets inducible gene expression to CNS progenitor cells,"PNAS USA. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Miyama,S: "Continuity with Ganglionic Eminence Modulates Interkinetic Nuclear Migration in the Neocortical Pseudostratified Ventricular Epithelium."Exp.Neurol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Verney,C: "Independent controls for neocortical neuron production and histogenetic cell death."Dev.Neurosci. 22. 125-138 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi,T: "Sequence of neuron origin and neocortical laminar fate : relation to cell cycle of origin in the developing murine cerebral wall."J.Neurosci. 19. 10357-10371 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Delalle,I: "Cyclin E - p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE : A quantitative analysis of mRNA in-situ hybridization."Cereb Cortex. 9. 824-832 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] TAkahashi,T: "Proliferative behavior of the murine cerebral wall in tissue culture : cell cycle kinetics and checkpoints."Exp.Neurol. 156. 407-417 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayuki Mitsuhashi: "Overexpression of p27Kip1 lengthens G1-phase in a mouse model that targets inducible gene expression to CNS progenitor cells"PNAS. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sahoko Miyama: "Continuity with Ganglionic Eminence Modulates Interkinetic Nuclear Migration in the Neocortical Pseudostratified Ventricular Epithelium."Experimental Neurology. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Verney C: "Independent controls for neocortical neuron production and histogenetic cell death."Dev Neurosci. 22. 125-138 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T: "Sequence of neuron origin and neocortical laminar fate : relation to cell cycle of origin in the developing murine cerebral wall."J Neurosci. 19 (23). 10357-10371 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Delalle I: "Cycline E-p27 opposition and regulation of the G1 phase of the cell cycle in the murine neocortical PVE : A quantitative analysis of mRNA in-situ hybridization."Cerebral Cortex.. 9 (8). 824-832 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T: "Proliferative behavior of the murine cerebral wall in tissue culture : cell cycle kinetics and checkpoints"Experimental Neurology. 156. 407-417 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi T: "Cell cycle as operational unit of neocortical neuronogenesis"Neuroscientist. 5 (3). 155-163 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Caviness VS Jr: "The G1 restriction point as critical regulator of neocortical neurogenesis."Neurochem Res. 24 (4). 497-506 (1999)

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

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Published: 2002-03-26  

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