• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Regulation of force-dependent signal pathways during ectodermal patterning in Xenopus embryo

Research Project

Project/Area Number 21K06183
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Michiue Tatsuo  東京大学, 大学院総合文化研究科, 教授 (10282724)

Co-Investigator(Kenkyū-buntansha) 山元 孝佳  東京大学, 大学院総合文化研究科, 助教 (70724699)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords外胚葉パターニング / アフリカツメガエル / 物理的な力 / プラコード / 細胞張力 / ツメガエル / 力 / 予定プラコード / ヒトiPS細胞 / 胚パターニング / 細胞内シグナル伝達
Outline of Research at the Start

胚発生において、神経・表皮をはじめとする外胚葉パターンの形成には細胞内シグナル伝達経路が重要な役割を果たしている。同時に、細胞には様々な物理的な力がかかっており、両者の関係が強く示唆される。本研究では、これら三者間の因果関係の有無を直接調べるとともに領域特異的な力の発生の根拠を探ることで、どのような分子機構で細胞張力がシグナル経路を制御し、胚パターンを規定するのかを明らかにする。

Outline of Final Research Achievements

The aim of this study was to clarify the involvement of force in ectodermal patterning and its molecular mechanism. 1) Stretching stimuli on ectoderm tissues, centrifugal stimuli on gastrula embryos, and ectopic induction of apical contraction increased the expression of neural crest markers, whereas cell tension release by myosin inhibition or membrane scramblase injection reduced their expressions. These results suggest the involvement of force in neural crest formation. Furthermore, we demonstrated that force application enhanced both Wnt and BMP signaling. 2) We investigated the stiffness of ectoderm by suction measurement and AFM analysis, and found that the elasticity near the midline was higher than that of the lateral regions. 3) We demonstrated that the force application enhanced the placode gene expression in neural cells differentiated from human iPS cells.

Academic Significance and Societal Importance of the Research Achievements

これまで詳細が明らかではなかった、初期胚の外胚葉パターニングに力が関与すること、またその根拠の一つして外胚葉におけるWnt・BMPシグナルが力依存的に活性化することを示した点は、学術的な意義が非常に大きい。また、胚にかかる力が外胚葉の領域ごとに異なる理由として外胚葉領域の剛性に着目し、一連の解析から実際に胚の正中線と側方部で剛性が異なることを示したことは、パターニングに関与する力がどのように発生するかを解く手がかりとなる。ヒトiPS細胞の結果も併せ、本課題で得られた成果は、将来ヒト幹細胞から個体構築を目指す上で、基盤となる情報を与えることになるだろう。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (28 results)

All 2024 2023 2022 2021 Other

All Journal Article (14 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 14 results,  Open Access: 6 results) Presentation (12 results) (of which Invited: 1 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Enhancement of neural crest formation by mechanical force in Xenopus development.2024

    • Author(s)
      Kaneshima T, Ogawa M, Yamamoto T, Tsuboyama Y, Miyata Y, Kotani M, Okajima T, Michiue T.
    • Journal Title

      Int. J. Dev. Biol

      Volume: 68 Issue: 1 Pages: 25-37

    • DOI

      10.1387/ijdb.230273tm

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Pancreatic β-cell Differentiation Efficiency of Human iPSC Lines for Clinical Use.2024

    • Author(s)
      Horikawa A, Tsuda K, Yamamoto T, Michiue T.
    • Journal Title

      Curr Stem Cell Res Ther.

      Volume: - Issue: 11 Pages: 1449-1460

    • DOI

      10.2174/011574888x267226231126185532

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of tumor-related genes via RNA sequencing of tumor tissues in Xenopus tropicalis2023

    • Author(s)
      Kitamura Kazuki、Yamamoto Takayoshi、Ochi Haruki、Suzuki Makoto、Suzuki Nanoka、Igawa Takeshi、Yoshida Tadashi、Futakuchi Mitsuru、Ogino Hajime、Michiue Tatsuo
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 13214-13214

    • DOI

      10.1038/s41598-023-40193-7

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Chemical inhibitors of cyclin-dependent kinase (CDKi) improve pancreatic endocrine differentiation of iPS cells.2023

    • Author(s)
      Ning H, Horikawa A, Yamamoto T, Michiue T.
    • Journal Title

      In Vitro Cell Dev Biol Anim.

      Volume: 59 Issue: 6 Pages: 410-419

    • DOI

      10.1007/s11626-023-00776-0

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Heparan sulfate modification enzyme, Hs6st1, is essential for neuroectodermal patterning in Xenopus embryos.2023

    • Author(s)
      Yamamoto T, Kaneshima T, Tsukano K, Michiue T
    • Journal Title

      Dev. Biol.

      Volume: 496 Pages: 87-94

    • DOI

      10.1016/j.ydbio.2023.01.011

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ccl19 and ccl21 affect cell movements and differentiation in early Xenopus development2023

    • Author(s)
      Goto T, Michiue T, Shibuya H.
    • Journal Title

      Dev. Growth. Diff.

      Volume: 65 Issue: 3 Pages: 175-189

    • DOI

      10.1111/dgd.12847

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ndst1, a heparan sulfate modification enzyme, regulates neuroectodermal patterning by enhancing Wnt signaling in Xenopus2023

    • Author(s)
      Yamamoto T, Kambayashi Y, Tsukano K, Michiue T.
    • Journal Title

      Dev. Growth. Diff.

      Volume: 65 Issue: 3 Pages: 153-160

    • DOI

      10.1111/dgd.12843

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Unidirectional tissue tension instructs planar cell polarity via cell elongation2022

    • Author(s)
      Hirano S, Mii Y, Charras G, Michiue T
    • Journal Title

      Development

      Volume: 149 Issue: 12

    • DOI

      10.1242/dev.200515

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Xenopus Dusp6 modulates FGF signaling to precisely pattern pre-placodal ectoderm2022

    • Author(s)
      Tsukano K, Yamamoto T, Watanabe T, Michiue T
    • Journal Title

      Dev. Biol.

      Volume: 488 Pages: 81-90

    • DOI

      10.1016/j.ydbio.2022.05.009

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive feedback regulation of frizzled-7 expression robustly shapes a steep Wnt gradient in Xenopus heart development, together with sFRP1 and heparan sulfate2022

    • Author(s)
      Yamamoto T, Kambayashi Y, Afouda B, Otsuka Y, Ciuraniuc C, Michiue T, Hoppler S
    • Journal Title

      elife

      Volume: 11

    • DOI

      10.7554/elife.73818

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Feedback regulation of signaling pathways for precise pre-placodal ectoderm formation in vertebrate embryos2022

    • Author(s)
      Michiue T, Tsukano K
    • Journal Title

      J. Dev. Biol

      Volume: 10 Issue: 3 Pages: 35-35

    • DOI

      10.3390/jdb10030035

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] <i>ccr7</i> affects both morphogenesis and differentiation during early <i>Xenopus</i> embryogenesis2022

    • Author(s)
      Goto Toshiyasu、Michiue Tatsuo、Shibuya Hiroshi
    • Journal Title

      Development, Growth &amp; Differentiation

      Volume: 64 Issue: 5 Pages: 254-260

    • DOI

      10.1111/dgd.12790

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel cell segmentation method for developing embryos using machine learning.2021

    • Author(s)
      Ota R, Ide T, Michiue T.
    • Journal Title

      Dev. Growth. Diff.

      Volume: 63 Issue: 8 Pages: 406-416

    • DOI

      10.1111/dgd.12747

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A simple method of hiPSCs differentiation into insulin-producing cells is improved with vitamin C and RepSox.2021

    • Author(s)
      Horikawa A, Mizuo K, Tsuda K, Yamamoto T, Michiue T.
    • Journal Title

      PLoS ONE

      Volume: 16 Issue: 7 Pages: e0254373-e0254373

    • DOI

      10.1371/journal.pone.0254373

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 細胞外分子によるモルフォゲン分布制御2023

    • Author(s)
      山元孝佳、道上達男
    • Organizer
      第46回日本分子生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 力学的刺激がツメガエル神経胚の神経堤領域決定に及ぼす影響2023

    • Author(s)
      小川真生、金島時、山元孝佳、道上達男
    • Organizer
      第46回日本分子生物学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ツメガエル外胚葉パターニングにおける物理的な力の関与2023

    • Author(s)
      金島時、小川真生、山元孝佳、道上達男
    • Organizer
      第94回日本動物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Unidirectional tension acts cooperatively with Wnt to establish PCP2023

    • Author(s)
      Sayuki Hirano, Yusuke Mii, Guillaume Charras, Tatsuo Michiue
    • Organizer
      日本発生生物学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ツメガエル初期胚における外胚葉パターンの決定機構2023

    • Author(s)
      道上 達男
    • Organizer
      広島大学両生類研究センター記念シンポジウム
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] FGFリガンド量のゆらぎに強いパターン形成機構ーツメガエル予定プラコード形成におけるDusp6の機能解析ー2022

    • Author(s)
      塚野皓平、山元孝佳、渡邊朋子、道上達男
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 機械的刺激によるツメガエル神経堤形成の促進2022

    • Author(s)
      金島時、小川真生、山元孝佳、道上達男
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ヒトiPS細胞から予定プラコードへの分化における張力の関与2022

    • Author(s)
      キム スンテ、道上達男
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ネッタイツメガエルを用いた、がん形成関連遺伝子の網羅的探索2022

    • Author(s)
      北村和輝、山元孝佳、越智陽城、道上達男
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] Wnt-受容体フィードバックによるロバストな心膜形成―ウェットとドライの相補的アプローチ2022

    • Author(s)
      山元 孝佳、 上林 勇太、 大塚 祐太、 道上 達男、Stefan Hoppler
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] ツメガエル胚の神経領域決定における物理的な力な関与2021

    • Author(s)
      道上達男、金島時、小川真生、山元孝佳
    • Organizer
      日本動物学会年会
    • Related Report
      2021 Research-status Report
  • [Presentation] ツメガエル胚において機械的刺激を人為的に増減させる手法2021

    • Author(s)
      金島時
    • Organizer
      日本ツメガエル研究集会
    • Related Report
      2021 Research-status Report
  • [Book] 発生生物学 基礎から再生医療の応用まで2022

    • Author(s)
      道上達男
    • Total Pages
      196
    • Publisher
      裳華房
    • ISBN
      9784785358747
    • Related Report
      2022 Research-status Report
  • [Remarks] 平面内細胞極性の軸が張力によって制御されることを発見

    • URL

      https://www.c.u-tokyo.ac.jp/info/news/20220713-pr-sobun-01.pdf

    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi