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Mechanisms of medial-lateral axis formation and inner hair cell-outer hair cell differentiation in the cochlea

Research Project

Project/Area Number 19K09887
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56050:Otorhinolaryngology-related
Research InstitutionKyoto University of Advanced Science

Principal Investigator

Tateya Tomoko  京都先端科学大学, 健康医療学部, 教授 (10512311)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords有毛細胞 / 蝸牛 / 発生・分化 / 外有毛細胞 / 内有毛細胞
Outline of Research at the Start

哺乳類では成熟した有毛細胞は一度障害を受けると再生せず、このことが難聴の多くが治療困難である原因と考えられている。応募者はマウスを用いて有毛細胞を含む蝸牛感覚上皮の発生過程につき研究し、有毛細胞再生医療への応用を目指している。
応募者らの予備的研究(内有毛細胞と外有毛細胞の分化が、蝸牛発生初期のBmp4-Idシグナル伝達系を介した内側-外側軸形成に依拠していることを示した)を展開し、蝸牛の内側-外側軸形成と内有毛細胞-外有毛細胞分化の制御機構を解明することを目的としている。さらに、得られた知見をもとにして内有毛細胞と外有毛細胞の「作り分け」方法を開発し、蝸牛有毛細胞再生に応用したい。

Outline of Final Research Achievements

To elucidate the role of Bmp4 signaling in developing cochlear sensory epithelium, we focused on Id1-3, downstream factors of Bmp4, and found that the Id genes are required for cochlear morphogenesis and play an important role in organization of the cochlear peripheral compartment, including outer hair cells. Based on our results of RNA-Seq and RNA-Seq at other institutions, we have selected 6 candidate genes involved in the differentiation and maturation of inner and outer hair cells, and have started loss of function experiments. One of the candidate gene knockout mice showed abnormal hair cell development, suggesting that it is a more direct regulator.

Academic Significance and Societal Importance of the Research Achievements

治療法のない難聴の殆どが蝸牛有毛細胞の障害を原因としており、聴覚再生に向けた研究の多くが有毛細胞の再生を目的としてきた。蝸牛の内有毛細胞と外有毛細胞は機能も異なり、内有毛細胞が聴覚情報を中枢に伝え、外有毛細胞は聴覚情報の増幅器として機能する。また、外有毛細胞はとりわけ、障害を受けやすいことが知られている。内有毛細胞と外有毛細胞の分化メカニズムを解明することは、聴覚再生研究の基礎として重要と考えられる。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019

All Journal Article (5 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (2 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Retrograde ERK activation waves drive base-to-apex multicellular flow in murine cochlear duct morphogenesis2021

    • Author(s)
      Ishii M, Tateya T, Matsuda M, Hirashima T.
    • Journal Title

      eLife

      Volume: 10 Pages: 1-16

    • DOI

      10.7554/elife.61092

    • NAID

      120006976053

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stalling interkinetic nuclear migration in curved pseudostratified epithelium of developing cochlear duct2021

    • Author(s)
      Ishii M., Tateya T., Matsuda M. and Hirashima T.
    • Journal Title

      Royal Society Open Science

      Volume: 8 Issue: 12 Pages: 211024-211024

    • DOI

      10.1098/rsos.211024

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Id genes are required for morphogenesis and cellular patterning in the developing mammalian cochlea2020

    • Author(s)
      Sakamoto Susumu、Tateya Tomoko、Omori Koichi、Kageyama Ryoichiro
    • Journal Title

      Developmental Biology

      Volume: 460 Issue: 2 Pages: 164-175

    • DOI

      10.1016/j.ydbio.2019.12.006

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Three-dimensional live imaging of Atoh1 reveals the dynamics of hair cell induction and organization in the developing cochlea2019

    • Author(s)
      Tateya Tomoko、Sakamoto Susumu、Ishidate Fumiyoshi、Hirashima Tsuyoshi、Imayoshi Itaru、Kageyama Ryoichiro
    • Journal Title

      Development

      Volume: 146 Issue: 21 Pages: 177881-177881

    • DOI

      10.1242/dev.177881

    • NAID

      120006770219

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 喉頭の発生(総説)2019

    • Author(s)
      楯谷 智子 楯谷 一郎 大森 孝一
    • Journal Title

      耳鼻臨床

      Volume: 112 Pages: 481-487

    • Related Report
      2019 Research-status Report
  • [Presentation] Bmp4-Id signaling regulates medial-lateral axis formation in developing cochlear epithelium.2019

    • Author(s)
      Susumu Sakamoto; Tomoko Tateya; Koichi Omori; Ryoichiro Kageyama.
    • Organizer
      The Association for Research in Otolaryngology 42nd MidWinter Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Multi-directional signals regulate the dynamics of cochlear hair cell induction and organization.2019

    • Author(s)
      Tomoko Tateya; Susumu Sakamoto; Fumiyoshi Ishidate; Tsuyoshi Hirashima; Itaru Imayoshi; Ryoichiro Kageyama.
    • Organizer
      The Association for Research in Otolaryngology 42nd MidWinter Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-04-18   Modified: 2024-01-30  

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