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Molecular basis of Zic-mediated developmental control

Research Project

Project/Area Number 16390086
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General medical chemistry
Research InstitutionRIKEN

Principal Investigator

ARUGA Jun  RIKEN BSI, Laboratory for Comparative.Neurogenesis, Laboratory Head, 比較神経発生研究チーム, チームリーダー (10232076)

Co-Investigator(Kenkyū-buntansha) ISHIGURO Akira  RIKEN BSI, Laboratory for Comparative.Neurogenesis, Research Scientist, 比較神経発生研究チーム, 研究員 (70373264)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2004: ¥7,400,000 (Direct Cost: ¥7,400,000)
KeywordsZic / transcription factor / cell differentiation / neural development / gene targeting / transcriptional complex / protein modification / congenital anomaly / zincフィンガータンパク質 / タンパク質間相互作用 / 遺伝子発現制御 / 転写調節 / 動物発生 / 構造生物学 / zincフィンガー / 蛋白質間相互作用 / 遺伝子発現調節 / 細胞内局在
Research Abstract

Zic genes are known for causal genes of holoprosencephaly, Dandy-Walker malformation, and heterotasxy.. In this study, following points of the Zic gene family have been dealt with. (1) Identification of novel Zic-binding proteins, (2) The biological significance of the protein-to-protein interaction between Zic and Zic-binding proteins, (3) Post-translational modification of Zic proteins, (4) Bio-signals that have contact points with Zic proteins.
Following points were revealed and publicized in the scientific community.
(1) Identification of novel two Zic2-containing high-molecular-weight molecular complexes (Ishiguro et al.,2007). Identification of I-mfa as a Zic-repressor by yeast two-hybrid screening. (2,3) Identification of a Zic2-kinase in the HMW molecular complexes. The phosphorylation of Zic2 protein was shown to be critical in the transcriptional regulatory processes. Other modifications sites in Zic proteins have been identified and characterized by mass spectrometry analysis. (4) The Zic related bio-signals was investigated by analyzing the Zic1/3 and Zic2/3 compound mutant mice (Inoue et al., 2007a; 2007b). In particular, we revealed that Zic1 and Zic3 have critical roles in the expansion of forebrain neuronal precursors. Wnt signals was suggested to be involved in the Zic mediated developmental control. In addition, functional similarity and difference among vertebrates Zic genes have been investigated in mouse and Xenopus (Ishiguro et al.,2004; Fujimi et al.,2006).

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (23 results)

All 2007 2006 2005 2004

All Journal Article (22 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly(ADP-ribose) polymerase, and RNA helicase A.2007

    • Author(s)
      Ishiguro A, Ideta M, Mikoshiba K, Chen DJ, Aruga J
    • Journal Title

      J Biol Chem 282

      Pages: 9983-9995

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Zic1 and Zic3 regulate medial forebrain development through expansion of neuronal progenitors.2007

    • Author(s)
      Inoue T, Ota M, Ogawa M, Mikoshiba K, Aruga J
    • Journal Title

      J Neurosci 27

      Pages: 5461-5473

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Zic2 and Zic3 synergistically control neurulation and segmentation of paraxial mesoderm in mouse embryo.2007

    • Author(s)
      Inoue T, Ota M, Mikoshiba K, Aruga J
    • Journal Title

      Dev Biol. (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elucidation of penetrance variability of a ZIC3 mutation in a family with complex heart defects and functional analysis of ZIC3 mutations in the first zinc finger domain.2007

    • Author(s)
      Chhin B, Hatayama M, Bozon D, Ogawa M, Schon P, Tohmonda T, Sassolas F, Aruga J, et al.
    • Journal Title

      Hum Mutat 28

      Pages: 563-570

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ZIC2-dependent transcriptional regulation is mediated by DNA-dependent protein kinase, poly (ADP-ribose) polymerase, and RNA helicase A.2007

    • Author(s)
      Ishiguro A, Ideta M, Mikoshiba K, Chen DJ, Aruga J
    • Journal Title

      J Biol Chem 282

      Pages: 9983-9995

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Elucidation of penetrance variability of a ZIC3 mutation in a family with complex heart defects and functional analysis of ZIC3 mutations in the first zinc finger domain.2007

    • Author(s)
      Chhin B, Hatayama M, Bozon D, Ogawa M, Schon P, Tohmonda T, Sassolas F, Aruga J, Valard AG, Chen SC, Bouvagnet P
    • Journal Title

      Hum Mutat 28

      Pages: 563-570

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A wide-range phylogenetic analysis of Zic proteins : implications for correlations between protein structure conservation and body plan complexity.2006

    • Author(s)
      Aruga J, Kamiya A, Takahashi H, Fujimi TJ, Shimizu Y, et al.
    • Journal Title

      Genomics 87

      Pages: 783-792

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Xenopus Zic4 : conservation and diversification of expression profiles and protein function among the Xenopus Zic family.2006

    • Author(s)
      Fujimi TJ, Mikoshiba K, Aruga J
    • Journal Title

      Dev Dyn 235

      Pages: 3379-3386

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A wide-range phylogenetic analysis of Zic proteins : implications for correlations between protein structure conservation and body plan complexity.2006

    • Author(s)
      Aruga J, Kamiya A, Takahashi H, Fujimi TJ, Shimizu Y, Ohkawa K, Yazawa S, Umesono Y, Noguchi H, Shimizu T, Saitou N, Mikoshiba K, Sakaki Y, Agata K, Toyoda A
    • Journal Title

      Genomics 87

      Pages: 783-792

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A wide-range phylogenetic analysis of Zic proteins, implications for correlations between protein structure conservation and body plan complexity.2006

    • Author(s)
      J.Aruga et al.
    • Journal Title

      Genomics (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] IP3 receptor types 2 and 3 mediate exocrine secretion underlying energy metabolism2006

    • Author(s)
      A.Futatsugi et al.
    • Journal Title

      Science 309

      Pages: 2232-2234

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Locomotor and oculomotor impairment associated with cerebellar dysgenesis in Zic3-deficient (Bent tail) mutant mice.2004

    • Author(s)
      Aruga J, Ogura H, Shutoh F, Ogawa M, Franke B, Nagao S, Mikoshiba K
    • Journal Title

      Eur J Neurosci 20

      Pages: 2159-2167

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The role of Zic genes in neural development.2004

    • Author(s)
      Aruga J
    • Journal Title

      Mol Cell Neurosci 26

      Pages: 205-221

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives.2004

    • Author(s)
      Inoue T, Hatayama M, Tohmonda T, Itohara S, Aruga J, Mikoshiba K
    • Journal Title

      Dev Biol. 270

      Pages: 146-162

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular properties of Zic4 and Zic5 proteins : functional diversity within Zic family.2004

    • Author(s)
      Ishiguro A, Inoue T, Mikoshiba K, Aruga J
    • Journal Title

      Biochem Biophys Res Commun 324

      Pages: 302-307

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Myogenic repressor I-mfa interferes with the function of Zic family proteins.2004

    • Author(s)
      Mizugishi K, Hatayama M, Tohmonda T, Ogawa M, Inoue T, Mikoshiba K, Aruga J
    • Journal Title

      Biochem Biophys Res Commun 320

      Pages: 233-240

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives.2004

    • Author(s)
      Inoue T, Hatayama M, Tohmonda T, Itohara S, Aruga J, Mikoshiba K
    • Journal Title

      Dev Biol 270

      Pages: 146-162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Mouse Zic5 deficiency results in neural tube defects and hypoplasia of cephalic neural crest derivatives.2004

    • Author(s)
      Inoue T et al.
    • Journal Title

      Dev Biol. 270

      Pages: 146-162

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Locomotor and oculomotor impairment associated with cerebellar dysgenesis in Zic3-deficient (Bent-tail) mutant mice.2004

    • Author(s)
      Aruga, J et al.
    • Journal Title

      Eur.J.Neurosci 20

      Pages: 2159-2167

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The role of Zic genes in neural development.2004

    • Author(s)
      Aruga, J
    • Journal Title

      Mol Cell Neurosci. 26

      Pages: 205-221

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Myogenic repressor I-mfa interferes with the function of Zic family proteins.2004

    • Author(s)
      Mizugishi, K. et al.
    • Journal Title

      Biochem Biophys Res Commun. 320

      Pages: 233-240

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Molecular properties of Zic4 and Zic5 proteins : functional diversity within Zic family.2004

    • Author(s)
      Ishiguro, A. et al.
    • Journal Title

      Biochem Biophys Res Commun. 324

      Pages: 302-307

    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] 特許2005

    • Inventor(s)
      有賀 純
    • Industrial Property Rights Holder
      独立行政法人理化学研究所
    • Filing Date
      2005-05-27
    • Acquisition Date
      2006-12-07
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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