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Molecular mechanism of hematopoietic and cardiovascular development in zebrafish

Research Project

Project/Area Number 20570216
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

KAWAHARA Atsuo  National Cardiovascular Center Research Institute, 細胞生物学部, 室長 (10362518)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords器官形成 / 心臓発生 / ゼブラフィッシュ / 血管発生 / 変異体 / 原因遺伝子 / スフィンゴシン-1-リン酸 / 輸送体
Research Abstract

I aimed to reveal novel key molecules in vascular and cardiac development by the characterization of novel cardiovascular zebrafish mutants. In the ko095 mutants, aberrant branching of intersegmental vessels besides of the neural tube was observed. Further, the increased expression of VEGF (vascular endothelial growth factor), which is a key factor in angiogenesis, caused the excessive vascular remodeling in the ko095 mutant. I found that the gene responsible for the ko095 is Sars (Seryl-tRNA synthetase) that is known as an enzyme essential for protein synthesis: Sars possesses a novel function involved in angiogenesis. On the other hand, the ko157 mutant exhibited the impairment of cardiac progenitor migration, resulting in two hearts known as cardia bifida. I found that the gene responsible for the ko157 is a twelve-pass transmembrane-domain protein Spns2 (Spnster-like 2). Biochemical analysis of Spns2 presented that Spns2 functions as a transporter of a sphingolipid mediator, sphingosine-1-phosphate (S1P). Thus, I found that Sars and Spns2 play important roles in vascular and cardiac development in zebrafish, respectively.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (43 results)

All 2010 2009 2008 Other

All Journal Article (14 results) (of which Peer Reviewed: 6 results) Presentation (24 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Non-canonical activity of Seryl-tRNA synthetase is involved in vascular development2009

    • Author(s)
      Fukui H., Hanaoka R., Kawahara A.
    • Journal Title

      Circulation Research 104

      Pages: 1253-1259

    • Related Report
      2010 Final Research Report
  • [Journal Article] Noncanonical activity of seryl-tRNA synthetase and vascular development2009

    • Author(s)
      Kawahara A., Stainier D.Y.R.
    • Journal Title

      Trends in Cardiovascular Medicine 19

      Pages: 179-182

    • Related Report
      2010 Final Research Report
  • [Journal Article] Genetic dissection of cardiac progenitor migration2009

    • Author(s)
      川原敦雄, 川原敦雄
    • Journal Title

      Inflammation and Regeneration 29

      Pages: 324-328

    • NAID

      10026094114

    • Related Report
      2010 Final Research Report
  • [Journal Article] Transcriptional regulation of a myeloid-lineage specific gene lysozyme C during zebrafish myelopoiesis2009

    • Author(s)
      Kitaguchi T., Kawakami K., Kawahara A.
    • Journal Title

      Mechanisms of Development 126

      Pages: 314-323

    • Related Report
      2010 Final Research Report
  • [Journal Article] The sphingolipid transporter Spns2 functions in migration of zebrafish myocardial precursors2009

    • Author(s)
      Kawahara A., Nishi T., Hisano Y., Fukui H., Yamaguchi A., Mochizuki N.
    • Journal Title

      Science 323

      Pages: 524-527

    • Related Report
      2010 Final Research Report
  • [Journal Article] スフィンゴシン-1-リン酸(S1P)の輸送体であるSpns2は、心臓前駆細胞の移動を制御する2009

    • Author(s)
      川原敦雄、西毅、山口明人、望月直樹
    • Journal Title

      細胞工学 28

      Pages: 390-391

    • Related Report
      2010 Final Research Report
  • [Journal Article] Non-canonical activity of Seryl-tRNA synthetase is involved in vascular development2009

    • Author(s)
      Hajime Fukui, Ryuki Hanaoka, Atsuo Kawahara
    • Journal Title

      Circulation Research 104

      Pages: 1253-1259

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of a myeloid-lineage specific gene lysozyme C during zebrafish myelopoiesis2009

    • Author(s)
      Tetsuya Kitaguchi, Koichi Kawakami, Atsuo Kawahara
    • Journal Title

      Mechanisms of Development 126

      Pages: 314-323

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Genetic dissection of cardiac progenitor migration2009

    • Author(s)
      Atsuo Kawahara
    • Journal Title

      Inflammation and Regeneration 29

      Pages: 324-328

    • NAID

      10026094114

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Noncanonical activity of Seryl-transfer RNA synthetase and vascular development2009

    • Author(s)
      Atsuo Kawahara, Didier Y.R.Stanier
    • Journal Title

      Trends in Cardiovascular Medicine 19

      Pages: 179-182

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2009

    • Author(s)
      川原敦雄、西毅、山口明人、望月直樹
    • Journal Title

      細胞工学(スフィンゴシン-1-リン酸(S1P)の輸送体であるSpns2は、心臓前駆細胞の移動を制御する)

      Pages: 390-391

    • Related Report
      2009 Annual Research Report
  • [Journal Article] The sphingolipid transporter Spns2 functions in migration of zebrafish myocardial precursors2009

    • Author(s)
      Atsuo Kawahara, Tsuyoshi Nishi, Yu Hisano, Hajime Fukui, Akihito Yamaguchi, Naoki Mochizuki
    • Journal Title

      Science 323

      Pages: 524-527

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] meisl regulates the development of endothelial cells in zebrafish Biochem.2008

    • Author(s)
      Minehata K., Kawahara A., Suzuki K.
    • Journal Title

      Biophys.Res.Commun. 347

      Pages: 647-652

    • Related Report
      2010 Final Research Report
  • [Journal Article] meisl regulates the development of endothelial cells in zebrafish2008

    • Author(s)
      Kenichi Minehata, Atsuo Kawahara, Takeshi Suzuki
    • Journal Title

      Biochem. Biophys. Res. Commun. 347

      Pages: 647-652

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] スフィンゴシン-1-リン酸(S1P)の初期発生のおける役割2010

    • Author(s)
      川原敦雄
    • Organizer
      日本分子生物学会
    • Place of Presentation
      神戸
    • Year and Date
      2010-12-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Role of Sphingosin-1-phosphate (S1P) signaling during zebrafish embryogenesis2010

    • Author(s)
      川原敦雄
    • Organizer
      日本発生生物学会
    • Place of Presentation
      京都
    • Year and Date
      2010-06-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Involvement of Sphingosine-1-phosphate (S1P) signaling in cardiac morphogenesis2010

    • Author(s)
      川原敦雄
    • Organizer
      2^<nd> Joint Meeting of the French and Japanese Scoieties for Developmental Biology
    • Place of Presentation
      Paris, France
    • Year and Date
      2010-05-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Sphingosine-1-phosphate transporter Spns2 regulates cardiac morphogenesis2009

    • Author(s)
      川原敦雄、西毅、久野悠、山口明人、望月直樹
    • Organizer
      第32回日本分子生物学会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-12-11
    • Related Report
      2010 Final Research Report
  • [Presentation] Sphingosine-1-phosphate transporter Spns2 regulates cardiac morphogenesis2009

    • Author(s)
      川原敦雄, 西毅、久野悠、山口明人、望月直樹
    • Organizer
      第32回日本生物学会大会
    • Place of Presentation
      横浜市
    • Year and Date
      2009-12-11
    • Related Report
      2009 Annual Research Report
  • [Presentation] The Sphingosine-1-phosphate transporter Spns2 is involved in cardiac morphogenesis.2009

    • Author(s)
      川原敦雄、西毅、久野悠、山口明人、望月直樹
    • Organizer
      第31回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      吹田市
    • Year and Date
      2009-11-30
    • Related Report
      2010 Final Research Report
  • [Presentation] The Sphingosine-1-phosphate transporter Spns2 is involved in cardiac morphogenesis2009

    • Author(s)
      川原敦雄, 西毅、久野悠、山口明人、望月直樹
    • Organizer
      第31回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      吹田市
    • Year and Date
      2009-11-30
    • Related Report
      2009 Annual Research Report
  • [Presentation] Spns2はスフィンゴシン-1-リン酸(S1P)の細胞外への放出を制御する2009

    • Author(s)
      川原敦雄、西毅、久野悠、山口明人、望月直樹
    • Organizer
      第82回日本生化学会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-22
    • Related Report
      2010 Final Research Report
  • [Presentation] Spns2はスフィンゴシン-1-リン酸(S1P)の細胞外への放出を制御する2009

    • Author(s)
      川原敦雄, 西毅、久野悠、山口明人、望月直樹
    • Organizer
      第82回日本生化学会大会
    • Place of Presentation
      神戸市
    • Year and Date
      2009-10-22
    • Related Report
      2009 Annual Research Report
  • [Presentation] 心臓前駆細胞の移動を制御するスフィンゴシン-1-リン酸(S1P)輸送体:Spns22009

    • Author(s)
      川原敦雄、西毅、久野悠、山口明人、望月直樹
    • Organizer
      第51回日本脂質生化学会
    • Place of Presentation
      名古屋市
    • Year and Date
      2009-07-31
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] Sphingosine-1-phosphate transporter Spns2 regulates cardiac progenitor migration.2009

    • Author(s)
      川原敦雄
    • Organizer
      FASEB Summer Research Conferences
    • Place of Presentation
      Arizona, USA
    • Year and Date
      2009-07-02
    • Related Report
      2010 Final Research Report
  • [Presentation] Sphingosine-1-phosphate transporter Spns2 regulates cardiac progenitor migration2009

    • Author(s)
      川原敦雄
    • Organizer
      FASEB Summer Research Conferences
    • Place of Presentation
      Arizona, USA
    • Year and Date
      2009-07-02
    • Related Report
      2009 Annual Research Report
  • [Presentation] Zebrafish Spns2 functioning as an S1P transporter is essential for the myocardial precursor migration.2009

    • Author(s)
      川原敦雄
    • Organizer
      第4回iCeMS国際シンポジウム
    • Place of Presentation
      京都市
    • Year and Date
      2009-05-28
    • Related Report
      2010 Final Research Report
  • [Presentation] Zebrafish Spns2 functioning as a S1P transporter is essential for the myocardial precursor migration2009

    • Author(s)
      川原敦雄
    • Organizer
      第4回 iCeMS国際シンポジウム
    • Place of Presentation
      京都市
    • Year and Date
      2009-05-28
    • Related Report
      2009 Annual Research Report
  • [Presentation] Zebrafish Spns2 functioning as an S1P transporter is essential for the myocardial precursor migration.2009

    • Author(s)
      川原敦雄
    • Organizer
      第5回武田科学財団シンポジウム
    • Place of Presentation
      東京都
    • Year and Date
      2009-05-26
    • Related Report
      2010 Final Research Report
  • [Presentation] Zebrafish Spns2 functioning as a S1P transporter is essential for the myocardial precursor migration2009

    • Author(s)
      川原敦雄
    • Organizer
      第5回武田科学財団シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      2009-05-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] The sphingolipid transporter Spns2 functions in migration of zebrafish myocardial precursors.2009

    • Author(s)
      川原敦雄
    • Organizer
      Keystone Symposium
    • Place of Presentation
      Carifornia, USA
    • Year and Date
      2009-04-26
    • Related Report
      2010 Final Research Report
  • [Presentation] The sphingolipid transporter Spns2 functions in migration of zebrafish myocardial precursors2009

    • Author(s)
      川原敦雄
    • Organizer
      Keystone Symposium
    • Place of Presentation
      California, USA
    • Year and Date
      2009-04-26
    • Related Report
      2009 Annual Research Report
  • [Presentation] 順遺伝学を用いたゼブラフィッシュの心臓・血管細胞の発生機構の解析2008

    • Author(s)
      川原敦雄
    • Organizer
      第29回日本炎症・再生医学会
    • Place of Presentation
      東京都
    • Year and Date
      2008-07-09
    • Related Report
      2010 Final Research Report
  • [Presentation] 順遺伝学を用いたゼブラフィッシュの心臓・血管細胞の発生機構の解析2008

    • Author(s)
      川原敦雄
    • Organizer
      第29回日本炎症・再生医学会
    • Place of Presentation
      東京
    • Year and Date
      2008-07-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Zebrafish spinster 2 involved in the migration of myocardial precursors in a novel regulator in sphingosine-1-phosphate (S1P) signaling.2008

    • Author(s)
      川原敦雄、西毅、山口明人、望月直樹
    • Organizer
      The zefrafish 2008 Conference
    • Place of Presentation
      Wisconsin, USA
    • Year and Date
      2008-06-27
    • Related Report
      2010 Final Research Report
  • [Presentation] Zebrafish spinster 2 involved in the migration of myocardial precursors is a novel regulator in sphingosine-1-phosphate (S1P) signaling2008

    • Author(s)
      川原敦雄, 西毅, 山口明人, 望月直樹
    • Organizer
      The zebrafish 2008 Conference
    • Place of Presentation
      Wisconsin University
    • Year and Date
      2008-06-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] Functional analysis of a novel zebrafish mutant that has defects in the migration of myocardial precursor cells.2008

    • Author(s)
      川原敦雄、望月直樹
    • Organizer
      日本発生生物学会第41回大会
    • Place of Presentation
      徳島市
    • Year and Date
      2008-05-28
    • Related Report
      2010 Final Research Report
  • [Presentation] Functional analysis of a novel zebrafish mutant that has defects in the migration of myocardial precursor cells2008

    • Author(s)
      川原敦雄, 望月直樹
    • Organizer
      日本発生生物学会第41回大会
    • Place of Presentation
      徳島
    • Year and Date
      2008-05-28
    • Related Report
      2008 Annual Research Report
  • [Book] 細胞:スフィンゴシン1-リン酸の輸送体2010

    • Author(s)
      川原敦雄
    • Publisher
      ニューサイエンス社
    • Related Report
      2010 Annual Research Report
  • [Remarks] ホームページ

    • URL

      http://www.ri.ncvc.go.jp/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      http://www.ri.ncvc.go.jp/

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] スフィンゴシン1-リン酸の新規トランスポーター分子2010

    • Inventor(s)
      望月直樹、川原敦雄、西毅、山口明人
    • Industrial Property Rights Holder
      国立循環器病研究センターと大阪大学
    • Patent Publication Number
      2010-077045
    • Filing Date
      2010-04-08
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] スフィンゴシン1-リン酸の新規トランスポーター分子2008

    • Inventor(s)
      望月直樹, 川原敦雄, 西毅, 山口明人
    • Industrial Property Rights Holder
      財団法人ヒューマンサイエンス財団、国立大学法人大阪大学
    • Industrial Property Number
      2008-245177
    • Filing Date
      2008-09-25
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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