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Molecular cascades underlying the integration of cell differentiation and morphogenesis in cranial/cardiac neural crest development

Research Project

Project/Area Number 16390218
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

KURIHARA Hiroki  The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (20221947)

Co-Investigator(Kenkyū-buntansha) KURIHARA Yukiko  The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (80345040)
AMANO Tomokazu  The University of Tokyo, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 寄付講座教員(助手相当) (50359634)
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)
KeywordsNeural crest cells / Pharyngeal arch / Cardiovascular development / Embryo genesis / Endothelin / Homeotic genes / Calpain / Transcriptional factors / 細胞内シグナル / 心血管発生 / 細胞分化 / 形態形成 / Dlx
Research Abstract

1.We have found that endothelin-1, produced by pharyngeal epithelium and core mesoderm, acts on cranial neural crest cells via ET-A receptor (ETAR) and determines the ventral identity of the anterior pharyngeal arches by inducing homeotic genes Dlx5 and Dlx6. After the regional specification by ET-1, Dlx5/6 expression was proved to be maintained by the FGF signaling.
2.We have found that the ET-1 signaling activates the enhancer activity of m5/6i, the intergenic element of the Dlx5/6loci, leading to the upregulation of Dlx5/6 expression.
3.We have established mice expressing GFP under the ETAR gene promoter to visualize the ETAR-expressing cells. We also realized the transgenic mouse system in which any genes of interest can be efficiently knocked-in into the ETAR locus by Cre recombinase-mediated cassette exchange. Using this system, we could knock-in the lacZgene to definitely identify the ETAR-expressing cells.
4.We have identified Capn6 as a gene downstream to the ET-1 signaling using DNA microarray. Capn6 was found to be possibly involved in cell division and morphology through the regulation of microtubular networks.
5.We have identified TAZ, a transcriptional coactivator, as a Pax3-binding protein. TAZ was found to coactivate the transcriptional activity of Pax3. TAZ-lacZ knock-in mice have identified TAZ expressing cells during embryogenesis. Partial lethality of TAZ-lacZ knock-in mice has indicated the importance of this gene in development.

Report

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

    (39 results)

All 2006 2005 2004

All Journal Article (39 results)

  • [Journal Article] Transcriptional activity of Pax3 is co-activated by TAZ.2006

    • Author(s)
      Murakami M
    • Journal Title

      biochem. Biophys. Res. Commun. 339・2

      Pages: 533-539

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional activity of Pax3 is co-activated by TAZ.2006

    • Author(s)
      Murakami M
    • Journal Title

      Biochem. Biophys. Res.Commun. 339

      Pages: 533-539

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Transcriptional activity of Pax3 is co-activated by TAZ.2006

    • Author(s)
      Murakami M
    • Journal Title

      Biochem Biophys Res Commun. 339・2

      Pages: 533-539

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Resistin like moleculeβactivates MAPKs, suppresses indulin signaling in hepatocytes and induces diabetes, hyperlipidemia and fatty liver in transgenic mice on a high-fat diet.2005

    • Author(s)
      Kushiyama, A.
    • Journal Title

      J. Biol. Chem. 280・51

      Pages: 42016-42025

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.2005

    • Author(s)
      Nishiyama K
    • Journal Title

      Circulation 112・28

      Pages: 2840-2850

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Glycogen debranching enzyme association with β-subunit enhances AMP-activated protein kinase activity.2005

    • Author(s)
      Sakoda, H.
    • Journal Title

      Am J Physiol Endocrinol Metab 289

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel PKB/AKT-binding protein enhanced PKB kinase activity and regulates DNA synthesis2005

    • Author(s)
      Anai, M
    • Journal Title

      J. Biol. Chem. 280

      Pages: 18525-18535

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Serum concentrations of RELMb and g are elevated in high-fat diet fed an dobese db/db mice, with increased productions in intestinal tract and bone marrow.2005

    • Author(s)
      Shojima, N.
    • Journal Title

      Diabetologia 48・5

      Pages: 984-992

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fluvastatin ameliorates the hyperhomocysteinemia-induced endothelial dysfunction : the antioxidative properties of fluvastatin.2005

    • Author(s)
      Morita H
    • Journal Title

      Circ. J. 69

      Pages: 475-480

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of lectin-line oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice.2005

    • Author(s)
      Inoue K
    • Journal Title

      Circ. Res. 97

      Pages: 176-184

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.2005

    • Author(s)
      Shozu M
    • Journal Title

      J. Mol. Endocrinol. 35

      Pages: 343-355

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Resistin like moleculeβactivates MAPKs, suppresses insulin signaling in hepatocytes and induces diabetes, hyperlipidemia and fatty liver in transgenic mice on a high-fat diet.2005

    • Author(s)
      Kushiyama, A., T.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 42016-42025

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.2005

    • Author(s)
      Nishiyama K
    • Journal Title

      Circulation 112

      Pages: 2840-2850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] A novel PKB/AKT-binding protein enhanced PKB kinase activity and regulates DNA synthesis.2005

    • Author(s)
      Anai, M.
    • Journal Title

      J.Biol.Chem. 280

      Pages: 18525-18535

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fluvastatin ameliorates the hyperhomocysteinemia-induced endothelial dysfunction : the antioxidative properties of fluvastatin.2005

    • Author(s)
      Morita H
    • Journal Title

      Circ.J. 69

      Pages: 475-480

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice.2005

    • Author(s)
      Inoue K
    • Journal Title

      Circ.Res. 97

      Pages: 176-184

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] MADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.2005

    • Author(s)
      Shozu M
    • Journal Title

      J.Mol.Endocrinol. 35

      Pages: 343-355

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Serum concentrations of RELMb and g are elevated in high-fat diet fed and obese db/db mice, with increased productions in intestinal tract and bone marrow.2005

    • Author(s)
      Shojima, N.
    • Journal Title

      Diabetologia 48・5

      Pages: 984-992

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.2005

    • Author(s)
      Nishiyama K
    • Journal Title

      Circulation. 112・18

      Pages: 2840-2850

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet.2005

    • Author(s)
      Kushiyama A
    • Journal Title

      J Biol Chem. 280・51

      Pages: 42016-42025

    • Related Report
      2005 Annual Research Report
  • [Journal Article] ADAMTS-1 is involved in normal follicular development, ovulatory process and organization of the medullary vascular network in the ovary.2005

    • Author(s)
      Shozu M
    • Journal Title

      J Mol Endocrinol. 35・2

      Pages: 343-355

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Overexpression of lectin-like oxidized low-density lipoprotein receptor-1 induces intramyocardial vasculopathy in apolipoprotein E-null mice.2005

    • Author(s)
      Inoue K
    • Journal Title

      Circ Res. 97・2

      Pages: 176-184

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Glycogen debranching enzyme association with beta-subunit regulates AMP-activated protein kinase activity.2005

    • Author(s)
      Sakoda H
    • Journal Title

      Am J Physiol Endocrinol Metab. 289・3

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Serum concentrations of resistin-like molecules beta and gamma are elevated in high-fat-fed and obese db/db mice, with increased production in the intestinal tract and bone marrow.2005

    • Author(s)
      Shojima N
    • Journal Title

      Diabetologia. 48・5

      Pages: 984-992

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fluvastatin ameliorates the hyperhomocysteinemia-induced endothelial dysfunction : the antioxidative properties of fluvastatin.2005

    • Author(s)
      Morita H
    • Journal Title

      Circ J. 69・4

      Pages: 475-480

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A novel protein kinase B (PKB)/AKT-binding protein enhances PKB kinase activity and regulates DNA synthesis.2005

    • Author(s)
      Anai M
    • Journal Title

      J Biol Chem. 280・18

      Pages: 18525-18535

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression.2004

    • Author(s)
      Ieda M
    • Journal Title

      J. Clin. Invest. 113

      Pages: 876-884

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endothelin-1 regulates the dorsoventral branchial arch patterning in mice.2004

    • Author(s)
      Ozeki H
    • Journal Title

      Mech. Dev. 121

      Pages: 387-395

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Temporal requirement of signaling cascade involving endothelin-1/endothelin A receptor in branchial arch development.2004

    • Author(s)
      Fukuhara S
    • Journal Title

      Mech. Dev. 121

      Pages: 1223-1233

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Akt-dependent phosphorylation negatively regulates the transcriptional activity of dHAND by inhibiting the DNA binding activith.2004

    • Author(s)
      Murakami M
    • Journal Title

      Eur. J. Biochem. 271

      Pages: 3330-3339

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Differential cooperation between dHAND and three different E-proteins. Biochem. Biophys.2004

    • Author(s)
      Murakami M
    • Journal Title

      Res. Commun. 323

      Pages: 168-174

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Unique roles of G protein-coupled histamine H(2) and gastrin receptors in growth and differentiation of gastric mucosa.2004

    • Author(s)
      Fukushima, Y.
    • Journal Title

      Eur J Pharmacol. 502

      Pages: 243-252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endothelin-1 regulates the dorsoventral branchial arch patterning in mice.2004

    • Author(s)
      Ozeki H
    • Journal Title

      Mech.Dev. 121

      Pages: 387-395

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Temporal requirement of signaling cascade involving endothelin-1/endothelin A receptor in branchial arch development.2004

    • Author(s)
      Fukuhara S
    • Journal Title

      Mech.Dev. 121

      Pages: 1223-1233

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Akt-dependent phosphorylation negatively regulates the transcriptional activity of dHAND by inhibiting the DNA binding activity.2004

    • Author(s)
      Murakami M
    • Journal Title

      Eur.J.Biochem. 271

      Pages: 3330-3339

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Differential cooperation between dHAND and three different E-proteins.2004

    • Author(s)
      Murakami M
    • Journal Title

      Biochem.Biophys.Res.Commun. 323

      Pages: 168-174

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Endothelin-1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression.2004

    • Author(s)
      Ieda M
    • Journal Title

      J.Clin.Invest. 113

      Pages: 876-884

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endothelin- 1 regulates cardiac sympathetic innervation in the rodent heart by controlling nerve growth factor expression.2004

    • Author(s)
      Ieda M
    • Journal Title

      J.Clin.Invest. 113

      Pages: 876-884

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Temporal requirement of signaling cascade involving endothelin-1/endothelin A receptor in branchial arch development.2004

    • Author(s)
      Fukuhara S
    • Journal Title

      Mech.Dev 121

      Pages: 1223-1233

    • Related Report
      2004 Annual Research Report

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

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