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Molecular basis of Zic proteins-mediated developmental regulation.

Research Project

Project/Area Number 13480260
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionThe Institute of Physical and Chemical Research

Principal Investigator

ARUGA Jun  RIKEN, Laboratory for Developmental Neurobiology, Research Scientist, 発生神経生物研究チーム, 研究員 (10232076)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥15,100,000 (Direct Cost: ¥15,100,000)
Fiscal Year 2002: ¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 2001: ¥7,800,000 (Direct Cost: ¥7,800,000)
KeywordsZic / zinc finger protein / transcriptional regulation / neural development / protein-protein interaction / gene targetin / microarray analysis / mechanism of bio-signal transduction / 蛋白質・蛋白質間相互作用 / 転写因子 / 遺伝子発現調節 / 神経突起伸展制御 / 骨格形成 / 神経細胞分化 / 転写制御 / 脊髄 / 小脳 / トランスジェニックマウス
Research Abstract

In this research project, we investigated following subjects : 1.Clarification of signal transduction pathway controlling the funtion of Zic proteins. 2.Identification of the transcriptioin-activating domain in Zic proteins. 3.Identification of uncharacterized Zic-binding proteins. 4.Understanding the the regulatory mechanism of the identified protein-protein interactions and their significance in the developmental control. 5.Exploration and analysis of the downstream target genes of Zic proteins. As an achievement of the investigation, we revealed following facts : 1.Zic proteins can phycally and functionally interact with Gli proteins, which are the transcriptional mediator of the Hedgehog signal (Koyabu et al., 2001 ; Mizugishi et al., 2001), 2.Zic1 can activate the Notch signaling as indicated by the gain-of-function analysis of Zic1 in chick and mouse spinal cord (Aruga et al., 2002), 3.Novel transcription activating domains were mapped in the N terminal region and zinc finger domain of Zic2 proteins (Mizugishi et al., in press), 4.Severeal Zic-binding proteins was identified by yeast two hybrid assay. The role of interaction in skeletal morphogenesis was investigated as for one of the newly identified Zic proteins. 5.Candidates of the Zic 1 downstream target genes in the course of cerebellar development were identified by microarray analysis (Hoshino et al., 2004). The microarray analysis was also carried out using other Zic mutant mice. Some of the candidate genes were now cleared to be important in the regulation of neuronal development.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Aruga, J.: "The role of Zic genes in the neural development."Mol.Cell.Neurosci.. (印刷中). (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue, T., et al.: "Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives."Dev.Biol.. 270. 146-162 (2004)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Herrera, E. et al.: "Zic2 patterns binocular vision by specifying the uncrossed retinal projection."Cell. 114. 545-557 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aruga, J. et al.: "Zic2 controls the cerebellar development in cooperation with Zic1."J.Neurosci.. 22. 218-225 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aruga, J. et al.: "Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation."Dev.Biol.. 244. 329-341 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizugishi, K. et al.: "Molecular properties of Zic proteins as transcriptional regulators and their relationship to GLI proteins."T.Biol.Chem.. 276. 2180-2188 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aruga, J.: "The role of Zic genes in the neural development"Mol.Cell.Neurosci. (in press). (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Inoue, T., Hatayama, M., Tohmonda, T., Itohara, S., Aruga J., Mikoshiba, K.: "Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives."Dev.Biol.. 270. 146-162 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Herrera, E., Brown, L., Aruga, J., Rachel, R.A., Dolen, G., Mikoshiba, K., Brown, S., Mason, C.A.: "Zic2 patterns binocular vision by specifying the uncrossed retinal Projection"Cell. 114. 545-557 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aruga, J., Inoue, T., Hoshino, J., Mikoshiba: "Zic2 controls the cerebellar development in cooperation with Zic1."J.Neurosci.. 22. 218-225 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aruga, J., Tohmonda, I., Homma S., Mikoshiba K.: "Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation"Dev.Biol.. 244. 329-341 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizugishi, K., Aruga, J., Nakata, K., Mikoshiba, K.: "Molecular properties of Zic proteins as transcriptional regulators and their relationship to GL1 proteins."J.Biol.Chem.. 276. 2180-2188 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aruga, J. et al.: "Identification and characterization of Slitrk, a novel neruonal transmembrane protein family controlling neurite outgrowth"Mol.Cell.Neurosci.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Hoshino, J. et al.: "Dorzl, a novel gene expressed in differentiating cerebellar granule neurons, is down-regulated in Zic1-deficient mouse"Mol.Brain Res.. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitaguchi, T. et al.: "Xenopus Brachyury regulates mesodermal expression of Zic3, a gene controlling left-right asymmetry"Dev.Growth Diff.. 44. 55-61 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aruga, J. et al.: "Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation"Dev.Biol.. 244. 329-341 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aruga, J. et al.: "Zic2 controls the cerebellar development in cooperation with Zic1"J.Neurosci.. 22. 218-225 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aruga, J., Tohmonda, T., Homma S., Mikoshiba K.: "Zic1 promotes the expansion of dorsal neural progenitors in spinal cord by inhibiting neuronal differentiation"Dev. Biol.. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Aruga, J., Inoue, T., Hoshino, J., Mikoshiba, K.: "Zic2 controls the cerebellar development in cooperation with Zic1"J. Neurosci.. 22. 218-225 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ogura, H., Aruga, J., Mikoshiba, K.: "Behavioral abnormalities of Zic1 and Zic2 mutant mice : implications as models for human neurological disorders"Behav. Genet.. 31. 317-324 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitaguchi, T., Nakata, K., Nagai, T., Aruga, J.et al.: "Xenopus Polycomblike 2(XPcl2)controls anterior to posterior patterning of the neural tissue"Dev. Genes Evol.. 211. 309-314 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koyabu, Y., Nakata, K., Mizugishi K., Aruga, J.et al.: "Physical and functional interaction between Zic and Gli proteins"J. Biol Chem.. 276. 6889-6892 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mizugishi, K., Aruga, J., Nakata.K., Mikoshiba, K.: "、"J. Biol Chem.. 276. 2180-2188 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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