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The mechanism of mesenchymal cell polarity in mouse tracheal smooth muscle

Research Project

Project/Area Number 17K15133
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Developmental biology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Kishimoto Keishi  国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (70700029)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords気管 / 極性 / 間充織 / マウス / マウス気管 / 細胞極性 / 平滑筋
Outline of Final Research Achievements

In this study, we attempted to elucidate the mechanism of mesenchymal cell polarity toward epithelial tissue.Co-culture system of mesenchymal cells and epithelial cells revealed the directed migration of mesenchymal cells to epithelial cell spheroid, suggested that epithelial tissue secretes the factors inducing mesenchymal cell polarity. we next explored polarizing cues from epithelium and signal pathway activated in mesenchymal tissue at the onset of cell polarization. At E12.5 mouse embryos, Sonic hedgehog, Wnt4, Wnt7b was highly expressed in epithelial tissue of the trachea. Furthermore, the analyses of reporter mouse line showed these signaling pathway was remarkably activated in mesenchyme. Most importantly, loss of Wnt activity in mesenchyme disrupted mesenchymal cell polarity. These findings indicate that epithelial Wnt induces mesenchymal cell polarity in mouse embryonic trachea.

Academic Significance and Societal Importance of the Research Achievements

正しい臓器形態の構築には、細胞の空間的位置づけ、即ち、極性が必須である。申請者らはマウス気管平滑筋細胞が極性化し、平滑筋の配列や気管伸長を調節することを報告にしている。これまで細胞極性の研究は上皮細胞を中心に展開されてきた。上皮細胞は、頂端-基底の極性や平面内極性を保持し、組織に非対称性を与える。対して、間充織細胞の方向性を定義する機構については知られていなかった。本研究成果は、これまで言及されなかった間充織の極性の制御機構を明らかにするものである。また、間充織の極性化は食道でも観察されたことから、本研究で得られた知見は、他の臓器形成機構の理解にも貢献することが期待される。

Report

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

    (15 results)

All 2019 2018 2017 Other

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (9 results) (of which Int'l Joint Research: 3 results) Book (2 results) Remarks (2 results)

  • [Journal Article] Synchronized mesenchymal cell polarization and differentiation shape the formation of the murine trachea and esophagus2018

    • Author(s)
      Kishimoto, K., Tamura, M., Nishita, M., Minami, Y., Matsuoka, A., Abe, T., Shigeta, M., Morimoto, M.
    • Journal Title

      Nat. Commun.

      Volume: 9 Issue: 1 Pages: 2816-2816

    • DOI

      10.1038/s41467-018-05189-2

    • NAID

      120006496738

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The potassium channel KCNJ13 is essential for smooth muscle cytoskeletal organization during mouse tracheal tubulogenesis2018

    • Author(s)
      Yin Wenguang、Kim Hyun-Taek、Wang ShengPeng、Gunawan Felix、Wang Lei、Kishimoto Keishi、Zhong Hua、Roman Dany、Preussner Jens、Guenther Stefan、Graef Viola、Buettner Carmen、Grohmann Beate、Looso Mario、Morimoto Mitsuru、Mardon Graeme、Offermanns Stefan、Stainier Didier Y. R.
    • Journal Title

      Nature Communications

      Volume: 9 Issue: 1 Pages: 2815-2815

    • DOI

      10.1038/s41467-018-05043-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Synchronized mesenchymal cell polarization and differentiation shape the trachea2018

    • Author(s)
      Kishimoto K, and Morimoto M
    • Organizer
      Joint Annual Meeting of the Japanese Society of Developmental Biologists 51th and the Japan Society for Cell Biology 70th
    • Related Report
      2018 Annual Research Report
  • [Presentation] 気管の形態形成における間充織極性化の重要性2018

    • Author(s)
      岸本 圭史, 森本 充
    • Organizer
      日本呼吸器学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Orientated mesenchymal cell polarization and differentiation shape the trachea2018

    • Author(s)
      Keishi Kishimoto, Masaru Tamura, Michiru Nishita, Yasuhiro Minami and Mitsuru Morimoto
    • Organizer
      Keystone Symposia Endoderm Development and Disease: Cross-Organ Comparison and Interplay
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Orientated mesenchymal cell polarization and differentiation shape the trachea2018

    • Author(s)
      Keishi Kishimoto
    • Organizer
      Keystone Symposia Endoderm Development and Desease:Cross Organ Comparison and Interplay
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 気管の形態形成における間充織極性化の重要性2018

    • Author(s)
      岸本 圭史
    • Organizer
      第58回日本呼吸器学会学術講演会
    • Related Report
      2017 Research-status Report
  • [Presentation] Synchronized mesenchymal cell polarization and differentiation shape the trachea2018

    • Author(s)
      Keishi Kishimoto
    • Organizer
      the Joint Annual Meeting of 70th JSCB and 51st JSDB
    • Related Report
      2017 Research-status Report
  • [Presentation] Oriented mesenchymal cells drive tracheal tubulogenesis.2017

    • Author(s)
      Keishi Kishimoto
    • Organizer
      50th Annual Meeting of the Japanese Society of Developmental Biologists, 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Oriented mesenchymal cells drive tracheal tubulogenesis.2017

    • Author(s)
      Keishi Kishimoto
    • Organizer
      18th International Congress of Developmental Biology, 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Mesenchymal cell polarity and differentiation shape mouse airway2017

    • Author(s)
      Keishi Kishimoto
    • Organizer
      Consortium of Biological Sciences 2017
    • Related Report
      2017 Research-status Report
  • [Book] 決定版 オルガノイド実験スタンダード2019

    • Author(s)
      岸本 圭史、森本 充
    • Total Pages
      372
    • Publisher
      羊土社
    • ISBN
      9784758122399
    • Related Report
      2018 Annual Research Report
  • [Book] 実験医学2018年11月号2018

    • Author(s)
      岸本 圭史、森本 充
    • Total Pages
      145
    • Publisher
      羊土社
    • ISBN
      9784758125130
    • Related Report
      2018 Annual Research Report
  • [Remarks] 筋肉の隊列と軟骨の出現が気管を長く太くする

    • URL

      https://www.bdr.riken.jp/jp/news/2018/research005.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 管腔臓器の長さと太さが決まる仕組みを解明 -筋肉と軟骨が気管のサイズを決定していた-

    • URL

      http://www.riken.jp/pr/press/2018/20180726_3/

    • Related Report
      2018 Annual Research Report

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

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