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Analysis of establish and differentiation of pluripotent cell during pre-implantation mouse development

Research Project

Project/Area Number 17K14976
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Laboratory animal science
Research InstitutionShiga University of Medical Science

Principal Investigator

AZAMI TAKUYA  滋賀医科大学, 動物生命科学研究センター, 客員助教 (90793290)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords初期胚発生 / Fgf4 / FGF-ERK / エピブラスト / 原始内胚葉 / 内部細胞塊 / Klf5 / 分化 / 原子内胚葉 / FGF / ERK / 多能性 / 発生・分化 / 応用動物
Outline of Final Research Achievements

In preimplantation mouse development, ICM cells generate epiblast (EPI) which differentiate embryo proper and primitive endoderm (PrE) which differentiate embryonic yolk sac. Although FGF-ERK pathway plays pivotal roles in the differentiation of EPI and PrE, it is unclear how FGF-ERK pathway is regulated. In this study, we identified that Klf5 represses Fgf4 expression at E3.25 and maintain the balance of EPI and PrE. We developed the technique to stain FGF4 protein and phosphorylated ERK in the preimplantation embryo and analysed what kind of cells activate FGF-ERK pathway.

Academic Significance and Societal Importance of the Research Achievements

本研究ではKlf5がFgf4遺伝子を抑制することでエピブラスト(EPI)と原始内胚葉(PrE)の分化バランス維持していることを明らかにした。初期胚でFgf4の発現を誘導する因子はこれまで明らかにされているが、抑制する因子の報告はこれまでになく、FGF-ERK経路によるEPIとPrEの分化メカニズムの一端を明らかにする成果である。
これまでは初期胚におけるリン酸化ERKの染色は安定しないため、どの様な細胞でERK経路が活性化しているのかを解析することが困難だった。本研究で新たに確立した初期胚におけるリン酸化ERKの染色方法は、FGF-ERK経路による細胞分化を解析に広く応用できるものである。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Int'l Joint Research] オーベルニュ大学(フランス)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] オーベルニュ大学(フランス)

    • Related Report
      2017 Research-status Report
  • [Journal Article] Klf5 maintains the balance of primitive endoderm versus epiblast specification during mouse embryonic development by suppression of Fgf42017

    • Author(s)
      Azami Takuya、Waku Tsuyoshi、Matsumoto Ken、Jeon Hyojung、Muratani Masafumi、Kawashima Akihiro、Yanagisawa Jun、Manabe Ichiro、Nagai Ryozo、Kunath Tilo、Nakamura Tomonori、Kurimoto Kazuki、Saitou Mitinori、Takahashi Satoru、Ema Masatsugu
    • Journal Title

      Development

      Volume: 144 Issue: 20 Pages: 3706-3718

    • DOI

      10.1242/dev.150755

    • NAID

      120007134671

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Lineage specification during mouse preimplantation development controlled by Klf5 and FGF-ERK pathway.2018

    • Author(s)
      Takuya Azami
    • Organizer
      The 6th International Conference on Biology and Pathobiology of KLF/Sp Transcription Factors (KLF-2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Klf5はFgf4を抑制することによりEPIとPrEの分化バランスを維持する2017

    • Author(s)
      浅見拓哉, 和久 剛, 全 孝静, 松本 健, 高橋 智, 依馬 正次
    • Organizer
      第40回日本分子生物学会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2020-03-30  

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