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Roles of Wnt/β-catenin/TCF signal transduction pathway in early T cell development

Research Project

Project/Area Number 10670299
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

FUJIMOTO Shinji  KYOTO UNIVERSITY, Institute for Frontier Medical Sciences, Assistant, 再生医科学研究所, 助手 (60199370)

Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2000: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1999: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsmurine early T cell development / Wnt / Frizzled 3 / dominant negative form / retroviral vector / signal transduction / シグナル伝達経路 / ドミナントネガティプフォーム / T前駆細胞 / 造血系前駆細胞 / TCF / LEF-1 / Frizzled3 / β カテニン / RT-PCR
Research Abstract

Wnt/β-catenin/TCF signaling is important for murine early T cell development. However, our understanding of each transmitting molecule is incomplete. As the result of this study, a member of the Frizzled (Fz) family, Fz3, to which secreted Wnt protein binds, is revealed to be one of key factors in the pathway. I have also established a method efficiently transducing gene into murine hematopoietic progenitors.
The expression level of Fz genes in fetal and adult thymus was examined by RT-PCR.We found that Fz3 is exclusively transcribed in fetal thymocytes, and that the highest expression is observed at the developmental stage after which rearrangement of T cell receptor (TCR) β chain gene occurs. In order to investigate the function of Fz3 during early T cell development, a dominant negative form retaining only Fz3 extracellular domain (sFz3) was forced to express in hematopoietic progenitors and the cells were cultured under the conditions suitable for T cell development. For the transduction, a retroviral vector with GFP gene as a marker was used. The number of cells recovered after the culture was far less than that obtained from the vector-transduced sample. Surprisingly, immature CD3^-CD4^-CD8^-CD44^-CD25^+ T cells still existed in the sFz3-transduced sample. Additionally, Fz3 is not expressed in TCR^+ T cells. Taken together, my data strongly suggest that the signal mediated by Fz3 is indispensable for differentiation and proliferation of T progenitors which rearranged TCR β but not α chain gene, and that the signal is partly responsible for multiplying more primitive T progenitors with unrearranged TCR β chain loci. In the future, Wnt molecules that bind to Fz3 in the T progenitors should be determined. In addition, analysis of target genes regulated by the Fz3 signaling will be required to comprehend the molecular mechanisms of early T cell development.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kawamoto,H.: "Emergence of T cell progenitors without B cell or myeloid differentiation potential at the earliest stage of hematopoiesis in the murine fetal liver"J.Immunol.. 162. 2725-2731 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohmura,K.: "Emergence of T.B.and myeloid lineage-committed as well as multipotent hematopoietic progenitors in the aorta-gonad-mesonephros region of day 10 fetuses of the mouse"J.Immunol. 163. 4788-4795 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikawa,T: "Commitment of common T/natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay."J.Exp.Med. 190. 1617-1625 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamoto,H: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver."Immunity. 12. 441-450 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikawa,T: "Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2"Proc.Natl.Acad.Sci.USA. in press. (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 藤本真慈: "胸腺T細胞の分化に白血球特異的アダプター蛋白SLP-76が必要である"臨床免疫. 31. 710-716 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 田村隆明: "BioScience新用語ライブラリー転写因子第2版"羊土社. 227 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamoto, H., Ohmura, K., Fujimoto, S., and Katsura, Y.: "Emergence of T cell progenitors without B cell or myeloid differentation potential at the earliest stage of hematopoiesis in the murine fetal liver."J.lmmunol. 162. 2725-2731 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohmura, K., Kawamoto, H., Fujimoto, S., Ozaki, S., Nakao, K.and Kastura, Y.: "Emergence of T, B, and myeloid lineage-committed as well as multipotent hematopoietic progenitors in the aortagonad-mesonephros region of day 10 fetuses of the mouse."J.lmmunol.. 163. 4788-4795 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikawa, T., Kawamoto, H., Fujimoto, S.and Katsura, Y.: "Commitment of common T/natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay."J.Exp.Med.. 190. 1617-1625 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamoto, H., Ikawa, T., Ohmura, K.Fujimoto, S.and Katsura, Y.: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver."Immunity. 12. 441-450 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ikawa, T., Fujimoto, S., Kawamoto, H., Katsura, Y.and Yokota, Y.: "Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2."Proc.Natl.Acad.Sci.USA. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kawamoto,Hiroshi: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver"Immunity. 12・4. 441-450 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ikawa,Tomokatsu: "Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2"Proc.Natl.Acad.Sci.USA. (発表予定). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohmura,Koichiro: "Emergence of T,B, and myeloid lineage-committed as well as multipotent hematopoietic progenitors in the aorta-gonad-mesonephros region of day to fetuses of the mouse"The Journal of Immunology. 163・9. 4788-4795 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ikawa,Tomokatsu: "Commitment of common T/natural Killer(NK)pragenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor"The Journal of Experimental Medicine. 190・11. 1617-1626 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 藤本真慈: "胸腺T細胞の分化に白血球特異的アダプター蛋白SLP-76が必要である"臨床免疫. 31・6. 710-716 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamoto,Hiroshi: "T cell progenitors emerge earlier than B cell progenitors in the murine fetal liver"Immunity. (発表予定). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田村隆明: "Bio Science新用語ライブラリー 転写因子第2版"羊土社. 227 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawamoto,Hiroshi: "Emergence of T Cell Progeniters without β Cell or Myeloid Diferentiation Potential at the Earliest Stage of Hemictopeiesis in the Murin Fetal Liver" The Journal of Immunology. 162・5. 2725-2731 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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