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Regulation of hair cell microstructure and auditory function by Hippo pathway

Research Project

Project/Area Number 16K20274
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Otorhinolaryngology
Research InstitutionKeio University

Principal Investigator

Takanori Nishiyama  慶應義塾大学, 医学部(信濃町), 助教 (90627168)

Research Collaborator FUJIOKA Masato  
OISHI Naoki  
SAYA Hideyuki  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsLATS1 / Hippo経路 / 難聴 / 有毛細胞 / 内耳障害 / PCP / Lats1ノックアウト / 先天性内耳障害 / Lats1 / コルチ期 / 内耳性難聴 / 聴覚医学 / シナプス伝達 / 感音難聴
Outline of Final Research Achievements

Hippo pathway regulates organ size, self-renewal of stem cells, and cell differentiation. LATS1 and LATS2 participate in Hippo signaling pathway. We examined expression pattern of LATS1 and LATS2 in the mouse cochlea, particularly in the organ of Corti. Because we only found LATS1 expression in the organ of Corti, we next investigated Lats1 deficiency mice. We found LATS1 deficiency caused congenital hearing loss with abnormal polarity and stereocilia bundles in both inner and outer hair cells. Those phenotypes indicate the possibility of LATS1 relating to the inner ear development.

Academic Significance and Societal Importance of the Research Achievements

今までにHippo経路の構成蛋白の欠損による影響としては、組織の悪性腫瘍化や個体の体格の縮小など、細胞周期調節の異常に伴う変化として説明可能な変化であった。しかし、本研究で得られた表現型においては、先天性かつ持続的な内耳有毛細胞の異常であり、Hippo経路が発生段階に与える影響としての新たな側面が疑われる。また、LATS1が適切な細胞配列と関わる可能性があり、適正な内耳有毛細胞配列を規定する要因を明らかにすることは、内耳の再生や再現といった面でも重要と思われる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (5 results)

All 2018 2017 2016 Other

All Presentation (4 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Presentation] Hippo経路構成因子のLats1キナーゼ欠損がマウス内耳に与える影響の解析2018

    • Author(s)
      西山崇経
    • Organizer
      第28回日本耳科学会総会・学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Deficiency of Lats1 a configuration kinase of Hippo pathway causes congenital hearing loss in mice2018

    • Author(s)
      Takanori Nishiyama
    • Organizer
      55th Inner Ear Biology Workshop
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞周期調節経路破綻に伴う内耳への影響~Lats1キナーゼ欠損マウスの解析2017

    • Author(s)
      西山崇経
    • Organizer
      日本聴覚医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Hippo経路におけるLats1キナーゼ欠損による内耳機能・構造的影響の解析2016

    • Author(s)
      西山崇経
    • Organizer
      第117回日本耳鼻咽喉科学会学術講演会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2016-05-19
    • Related Report
      2016 Research-status Report
  • [Remarks] 慶應義塾大学医学部耳鼻咽喉科学教室研究紹介

    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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