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2006 Fiscal Year Final Research Report Summary

Spatio-temporal regulation of morphogenesis by heparan sulfate chains

Research Project

Project/Area Number 14082206
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionAichi Medical University

Principal Investigator

KIMATA Koji  Aichi Medical University, Institute medical Science, Professor (10022641)

Co-Investigator(Kenkyū-buntansha) HABUCHI Osami  Aichi University, Education, Professor (90024067)
HABUCHI Hiroko  Aichi Medical University, Institute for medical, Assistant Professor (90329821)
NAGAI Naoko  Aichi Medical University, Institute for medical Science, Research Associate (00367799)
Project Period (FY) 2002 – 2006
KeywordsHeparan sulfate / Cell growth factors / Morphogen / Concentration gradient / Chondroitin sulfate / Proteoglycans / Glycosaminoglycans / Mutant mouse
Research Abstract

Heparan sulfate (HS) whose basic backbone structure consists of repeating disaccharide of glucuronosyl glucosamine has astronomical number of different structures by sulfation at different positions and by isomerization of glucuronosyl residue. HS usually locates on the cell surfaces and in the extracellular matrix and its structure alters in a spacio-temporal manner. Most of secretary and soluble cell growth factors, cytokines and morphogens which are well known to be required for important cell activities such as cell proliferation, cell differentiation and cell morphology, for example, FGF and Wnt, have properties to bind to HS. Therefore, we hypothesized that those factors, when they differ, may bind to the HS portions with different structures specifically so that each activity of those factors could be regulated by HS distinctively. In this study we first clarified that different factors actually bind to HS with different O-sulfation positions. We then subjected moue, chicken, Zebrafish, and Drosophila to the alteration of genes for HS O-sulfation enzymes, and observed apparent abnormality of organogenesis and tissue-morphogensis in those animals. We further provided some evidence to show that the observed abnormality was due to altered signalings of those factors which were caused, by the abnormal changes in HS structure. Taken together, our study revealed the occurrence of regulation mechanisms of the activities of cell growth factors and morphogens by HS chains.

  • Research Products

    (26 results)

All 2007 2006 2005 2004 2003 2002

All Journal Article (19 results) Book (3 results) Patent(Industrial Property Rights) (4 results)

  • [Journal Article] Chondroitin sulfate N-acetylgalactosaminyltransferase-1 plays a critical role in chondroitin sulfate synthesis in cartilage.2007

    • Author(s)
      Sakai K
    • Journal Title

      J Biol Chem 282

      Pages: 4152-4161

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Essential role of heparan sulfate 2-0-sulfotransferase in chick limb bud patterning and development.2007

    • Author(s)
      Kobayashi T
    • Journal Title

      J Biol Chem 282

      Pages: 19589-19597

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Chondroitin sulfate N-acetylgalactosaminyltransferase-1 plays a critical role in chondroitin sulfate synthesis in cartilage.2007

    • Author(s)
      Sakai K, Kimata K, Sato T, Gotoh M, Narimatsu H, Shinomiya K, Watanabe H
    • Journal Title

      J Biol Chem 282

      Pages: 4152-4161

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Essential role of heparan sulfate 2-O-sulfotransferase in chick limb bud patterning and development.2007

    • Author(s)
      Kobayashi T, Habuchi H, Tamura K, Ide H, Kimata K
    • Journal Title

      J Biol Chem 282

      Pages: 19589-19597

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Knockout Mice and Proteoglycans. Comprehensive Glycoscience, - From Chemistry to Systems Biology (Ed.-in-Chief, J P Kamerling ; Subject Ed., A.Suzuki)2007

    • Author(s)
      Kimata K, Habuchi O, Habuchi H, Watanabe H
    • Journal Title

      Elsevier Vol 4

      Pages: 33

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling.2006

    • Author(s)
      Kamimura K, et al
    • Journal Title

      . J Cell Biol 174

      Pages: 773-778

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Versican/PG-M regulates chondrogenesis as an extracellular matrix molecule crucial for mesenchymal condensation.2006

    • Author(s)
      Kamiya N
    • Journal Title

      J Biol Chem 281

      Pages: 2390-2400

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Specific and flexible roles of heparan sulfate modifications in Drosophila FGF signaling.2006

    • Author(s)
      Kamimura K, Koyama T, Habuchi H, Ueda R, Masu M, Kimata K, Nakato H
    • Journal Title

      J Cell Biol 174

      Pages: 773-778

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Versican/PG-M regulates chondrogenesis as an extracellular matrix molecule crucial for mesenchymal condensation.2006

    • Author(s)
      Kamiya N, Watanabe H, Habuchi H, Takagi H, Shinomura T, Shimizu K, Kimata K
    • Journal Title

      . J Biol Chem. 281

      Pages: 2390-2400

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Heparin regulates vascular endothelial growth factorl65-dependentmitogenic activity, tube formation. and its receptor phosphorylation of human endothelial cells. Comparison of the effects of heparinand modified heparins.2005

    • Author(s)
      Ashikari-Hada S, et al
    • Journal Title

      J Biol Chem 280

      Pages: 31508-31515

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heparin regulates vascular endothelial growth factorl65-dependent mitogenic activity, tube formation, and its receptor phosphorylation of human endothelial cells. Comparison of the effects of heparin and modified heparins.2005

    • Author(s)
      Ashikari-Hada S, Habuchi H, Kariya Y, Kimata K
    • Journal Title

      J Biol Chem 174

      Pages: 31508-31515

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccharide library.2004

    • Author(s)
      Ashikari-Hada S, et al
    • Journal Title

      J Biol Chem 279

      Pages: 12346-12354

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Characterization of growth factor-binding structures in heparin/heparan sulfate using an octasaccharide library2004

    • Author(s)
      Ashikari-Hada S, Habuchi H, Kariya Y, Itoh N, Reddi AH, Kimata K
    • Journal Title

      J Biol Chem 279

      Pages: 12346-12354

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Enzymatic synthesis of chondroitin with a novel chondroitin sulfate N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis.2003

    • Author(s)
      Gotoh M, et al
    • Journal Title

      J Biol Chem 277

      Pages: 38189-38196

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heparan sulfate 6-o-sulfotransferase is essential for muscledevelopment in zebrafish.2003

    • Author(s)
      Bink RJ, et al
    • Journal Title

      J Biol Chem 278

      Pages: 31118-31127

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Molecular cloning and characterization of a novel human glycosyl-transferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities.2003

    • Author(s)
      Yada T, et al
    • Journal Title

      J Biol Chem 278

      Pages: 30235-30247

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Heparan sulfate 6-o-sulfotransferase is essential for muscle development in zebrafish.2003

    • Author(s)
      Bink RJ, Habuchi H, Lele Z, Dolk E, Joore J, Rauch QJ, Geisler R, Wilson SW, den Hertog J, Kimata K, Zivkovic D
    • Journal Title

      J Biol Chem 278

      Pages: 31118-31127

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Chondroitin sulfate synthase-2. Molecular cloning and characterization of a novel human glycosyltransferase homologous to chondroitin sulfate glucuronyltransferase, which has dual enzymatic activities.2003

    • Author(s)
      Yada T, Gotoh M, Sato T, Shionyu M, Go M, Kaseyama H, Iwasaki H, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Watanabe H, Narimatsu H, Kimata K
    • Journal Title

      J Biol Chem 278

      Pages: 30235-30247

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Enzymatic synthesis of chondroitin with a novel chondroitin sulfate N-acetylgalactosaminyltransferase that transfers N-acetylgalactosamine to glucuronic acid in initiation and elongation of chondroitin sulfate synthesis2002

    • Author(s)
      Gotoh M, Sato T, Akashima T, Iwasaki H, Kameyama A, Mochizuki H, Yada T, Inaba N, Zhang Y, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Nishihara S, Watanabe H, Kimata K, Narimatsu H
    • Journal Title

      J Biol Chem 277

      Pages: 38189-38196

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] Knockout Mice and Froteoglycans, Comprehensive Glycoscience, - From Chemistry to Systems Biology2007

    • Author(s)
      Kimata K
    • Total Pages
      33
    • Publisher
      Elsevier
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] chapter 4 Functions of proteoglycan/glycosaminoglycan in liver. Extracellular Matrix and the Liver2003

    • Author(s)
      Yada T, Koide N, Kimata K
    • Total Pages
      20
    • Publisher
      Elsevier Science
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] Chapter 4 Functions of proteoglycan/glycosaminoglycan in liver. Extracellular Matrix and the Liver.2003

    • Author(s)
      Yada T, Koide N, Kimata K
    • Total Pages
      20
    • Publisher
      Elsevier Science
    • Description
      「研究成果報告書概要(欧文)」より
  • [Patent(Industrial Property Rights)] ヘパラン硫酸6-O-硫酸基転移酵素2006

    • Inventor(s)
      羽渕弘子, 羽渕脩躬
    • Industrial Property Rights Holder
      生化学工業
    • Industrial Property Number
      特願 3818676
    • Acquisition Date
      2006-06-23
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] ノックアウト動物2005

    • Inventor(s)
      木全弘治, 羽渕弘子
    • Industrial Property Rights Holder
      生化学工業
    • Industrial Property Number
      特願 2005- 58162
    • Filing Date
      2005-03-10
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] ヘパラン硫酸 2-O-硫酸基転移酵素2005

    • Inventor(s)
      小林政, 羽渕弘子, 羽
    • Industrial Property Rights Holder
      生化学工業
    • Industrial Property Number
      特願 3672359
    • Acquisition Date
      2005-04-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 硫酸基転移酵素阻害剤2004

    • Inventor(s)
      木全弘治, 羽渕弘子
    • Industrial Property Rights Holder
      生化学工業
    • Industrial Property Number
      特願 2005-506231
    • Filing Date
      2004-11-25
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2010-06-09  

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