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Molecular mechanism of the formation and differentiation of hemangioblast

Research Project

Project/Area Number 16370095
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Developmental biology
Research InstitutionKyoto University

Principal Investigator

KAWAHARA Atsuo  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 科学技術振興助教授 (10362518)

Co-Investigator(Kenkyū-buntansha) HANAOKA Ryuki  Kyoto University, Graduate School of Medicine, Postdoctoral Fellow, 医学研究科, 科学技術振興研究員 (70362530)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2005: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2004: ¥7,100,000 (Direct Cost: ¥7,100,000)
Keywordszebrafish / hematopoietic development / functional analysis / hemangioblast / 造血・血管発生 / 新規機能遺伝子
Research Abstract

We have performed in situ-based screening to identify genes that are specifically expressed in the blood island where both blood and endothelial cells are generated. In this process, we have isolated the heme synthesis enzymes and further examined the function of CPO (coproporphyrinogen oxidase) during zebrafish erythrogenesis. Knockdown analysis of CPO using anti-sense morpholinos (CPO-MO) caused the strong suppression of hemoglobin production, and the maturation of erythorocyte is morphologically arrested. These results suggest that CPO plays important roles in zebrafish erythrogenesis. Next, we examined the regulation of CPO expression. In zebrafish, both GATA1 and biklf transcriptional factors are essential for the blood cell maturation. Interestingly, CPO promoter region has DNA binding sites for both factors. We found that CPO expression is strongly suppressed when biklf-morpholino was injected into vlt mutant embryos (lacking functional GATA1 gene). In contrast, CPO is ectopically induced when both GATA1 and biklf RNAs are injected into two-cell stage embryos. These results suggest that GATA1 and biklf cooperatively contribute the regulation of CPO expression.
We have additionally isolated a novel gene, b819 gene that is restrictedly expressed in the blood island. This gene has no homology to any known protein, but primary structure presents a possible membrane protein. Knockdown analysis of b819 gene induced the suppression of blood cells production and the disorganization of network formation of blood vessels. Since both blood and endothelial cells are produced from the common precursor "hemangioblast", b819 gene may be a critical regulator in this process. Further studies will be required to reveal how b819 gene contributes the development of blood and endothelial cells during early embryogenesis.

Report

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

    (4 results)

All 2006 2005

All Journal Article (4 results)

  • [Journal Article] Characterization of the heme synthesis enzyme coproporphyrinogen oxidase (CPO) in zebrafish erythrogenesis2006

    • Author(s)
      Ryuki Hanaoka, Shiori Katayama, Igor B.Dawid, Atsuo Kawahara
    • Journal Title

      Genes to Cells 11

      Pages: 293-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of the heme synthesis enzyme coproporphyrinogen oxidase (CPO) in zebrafish erythrogenesis2006

    • Author(s)
      Ryuki Hanaoka, Shiori Katayama, Igor B.Dawid, Atsuo Kawahara
    • Journal Title

      Genes to Cells vol.11

      Pages: 293-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Characterization of the heme synthesis enzyme coproporphyrinogen oxidase (CPO) in zebrafish erythrogensis2006

    • Author(s)
      Ryuki Hanaoka, Shiori Katayama, Igor B.Dawid, Atsuo Kawahara
    • Journal Title

      Genes to Cells 11

      Pages: 293-303

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Zebrafish GADD45β genes are involved in somite segmentation2005

    • Author(s)
      Atsuo Kawahara, Yong-Suk Che, Ryuki Hanaoka, Hiroyuki Takeda, Igor B.Dawid
    • Journal Title

      Proc.Natl.Acad.Sci.USA 102

      Pages: 361-366

    • Related Report
      2004 Annual Research Report

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

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