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The regulatory mechanism of proliferation and differentiation of the sensory precursor cells during inner ear development and its application for the regenerative medicine.

Research Project

Project/Area Number 20591983
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionOsaka University

Principal Investigator

MURATA Junko  Osaka University, 医学部, 准教授 (80332740)

Project Period (FY) 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords内耳発生 / 蝸牛 / 有毛細胞 / PI3K-Aktシグナル伝達系 / PTEN / Sensory Precursor Cell / 蝸牛神経説細胞 / PI3K-Akt伝達系 / 幹細胞 / 再生医療 / Notchシグナル伝達系 / 感覚上皮予定領域 / Hes1 / p27Kip1 / 細胞増殖 / 未分化性維持
Research Abstract

We tried to elucidate the regulatory mechanism of the proliferation and differentiation of the sensory progenitor cells during the mammalian inner ear development.
At first, we demonstrated the detailed expression patterns of Hes1 and the activated Notch1. In addition, we analyzed the developing inner ear of Hes1 knockout mice, and showed that Notch-Hes1 pathway contributes to the cochlear prosensory formation potentially through the transcriptional down regulation of p27Kip1 (Murata J et al., J Neurosci Res in 2009).
In 2008 and 2009 we investigated the developmental expression pattern of the phosphorylated Akt and PTEN, which is an antagonizing factor for the PI3K-Akt signaling pathway. We clarified that the immunoreactivity of PTEN is first observed within the prosensory region in the embryonic cochlear epithelium, and gradually restricted in the hair cell progenitors at the late embryonic stage.
The result implied that PI3K/Akt signaling pathway may function for the continuous proliferation and the pluripotency of the inner ear sensory precursor cells.
We also started functional analysis of PTEN in 2009, trying to generate inner ear specific PTEN conditional knockout mice. We introduced PTEN-flox mice from the laboratory of professor Tak-Mak in Toronto University and Foxg1-cre mice from Jackson Laboratory.
I was transferred from Osaka University to Juntendo University in July 2010. The frozen fertilize ova of the PTEN cko mice were also transferred to Juntendo University. We fused and individuated them and started to analyze the developing inner ear of PTEN cko mice.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (20 results)

All 2010 2009 2008 2001 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results) Presentation (12 results) Book (2 results) Remarks (1 results)

  • [Journal Article] 発生・分類・遺伝子 内耳の発生とそれに関与する遺伝子2009

    • Author(s)
      村田潤子
    • Journal Title

      JOHNS 第25巻第1号(総説)

      Pages: 21-26

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Notch-Hes1 pathway contributes to the cochlear prosensory formation potentially through the transcriptional down regulation of p27Kip1.2009

    • Author(s)
      Murata J, Ohtsuka T, Tokunaga A, Nishiike S, Inohara H, Okano H, Kageyama R
    • Journal Title

      J Neurosci Res. Dec;87(16)

      Pages: 3521-34

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Notch-Hes1 Pathway Contribute to the Cochlear Prosensory Formation Potentially Through the Transcriptional Down-Regulation of p27Kip12009

    • Author(s)
      Murata J, Ohtsuka T, Tokuaga A, Nishiike S, Inohara H, Okano H, Kageyama R
    • Journal Title

      Journal of Neuroscience Research 87

      Pages: 3521-3534

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 内耳の発生とそれに関与する遺伝子2009

    • Author(s)
      村田 潤子
    • Journal Title

      JHONS (東京医学社刊) 第2 5巻第1号

      Pages: 21-26

    • Related Report
      2008 Annual Research Report
  • [Journal Article] The Expression patterns of Phosphorylated Akt and PTEN in the Developing Cochlea2009

    • Author(s)
      Murata J, et al.
    • Journal Title

      Abstract of the 32nd Annual Midwinter Research Meeting of the ARO Vol. 32

      Pages: 258-258

    • Related Report
      2008 Annual Research Report
  • [Presentation] Transient Expression of PTEN in the Hair Cell and Neuronal Lineage During Mammalian Inner Ear Development2010

    • Author(s)
      Murata J, Kimura T, Tomiyama Y, Nishiike S, Doi K, Inohara H, Okano H, Nakano T
    • Organizer
      ARO 33rd MidWinter Meeting
    • Place of Presentation
      Disneyland Hotel (Anaheim, CA, USA)
    • Related Report
      2010 Final Research Report
  • [Presentation] Notch-Hes1 pathway may contribute to the cochlear prosensory formation through the transcriptional down-regulation of p27^<Kip1>2010

    • Author(s)
      Junko Murata, Toshiyuki Ohtsuka, Akinori Tokunaga, Kazusaku Kamiya, Hideyuki Okano, Katsuhisa Ikeda, Ryoichiro Kageyama
    • Organizer
      The 47^<th> Inner Ear Biology Workshop
    • Place of Presentation
      Prague in Czech Republic
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 神経節細胞での発現パターンを通じて考察したPI3K/Aktシグナル経路とPTENの内耳発生における役割について2010

    • Author(s)
      村田潤子、木村透、西池 季隆、太田有美、長谷川太郎、川島 貴之、池田勝久、猪原秀典、岡野栄之、仲野徹
    • Organizer
      第20回日本耳科学会学術講演会
    • Place of Presentation
      松山市
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] Transient Expression of PTEN inn the Hair Cell and Neuronal Lineage During Mammalian Inner Ear Development2010

    • Author(s)
      Murata J, Kimura T, Tomiyama Y, Nishiike S, Doi K, Inohara H, Okano H, Nakano T
    • Organizer
      ARO 33rd MidWinter Meeting
    • Place of Presentation
      Disneyland Hotel (Anaheim, CA, USA)
    • Related Report
      2009 Annual Research Report
  • [Presentation] The Expression Pattern of Phosphorylated Akt and PTEN in the Developing Cochlea.2009

    • Author(s)
      Junko Murata, Tohru Kimura, Suetaka Nishiike, Arata Horii, Toru Nakano, Hideyuki Okano
    • Organizer
      The 32^<nd> Annual Midwinter research Meeting of the ARO
    • Place of Presentation
      Baltimore Maryland, and U.S.A.
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス内耳発生異おけるPI3K/Aktシグナル経路の細胞増殖・生存促進機能について2009

    • Author(s)
      村田潤子、堀井新、森鼻哲生、土井勝美、西池季隆、猪原秀典、木村透、仲野徹、岡野栄之
    • Place of Presentation
      ザ・プリンスパークタワー東京
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス内耳発生異おけるPI3K/Aktシグナル経路の細胞増殖・生存促進機能について2009

    • Author(s)
      村田潤子、堀井新、森鼻哲生、土井勝美、西池季隆、猪原秀典、木村透、仲野徹、岡野栄之
    • Place of Presentation
      京王ホテル(東京)
    • Related Report
      2010 Final Research Report
  • [Presentation] 胎生期および生後マウス蝸牛でのリン酸化 Akt とPTENの発現について2009

    • Author(s)
      村田潤子, 堀井新, 森鼻哲生, 土井勝美, 西池季隆, 猪原秀典, 木村透, 仲野徹, 岡野栄之
    • Organizer
      第110回日本耳鼻咽喉科学会学術講演会
    • Place of Presentation
      ザ・プリンスパークタワー東京 (東京都)
    • Related Report
      2009 Annual Research Report
  • [Presentation] マウス内耳発生異おけるPI3K/Aktシグナル経路の細胞増殖・生存促進機能について2009

    • Author(s)
      村田潤子, 堀井新, 森鼻哲生, 土井勝美, 西池季隆, 猪原秀典, 木村透, 仲野徹, 岡野栄之
    • Organizer
      第19回日本耳科学会学術講演会
    • Place of Presentation
      京王ホテル (東京都)
    • Related Report
      2009 Annual Research Report
  • [Presentation] The Expression patterns of Phosphorylated Akt and PTEN in the Developing Cochlea2009

    • Author(s)
      Murata J., et al.
    • Organizer
      The 32nd Anull a 1 Midwinter Research Meeting of the ARO
    • Place of Presentation
      Baltimore, ML, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] 胎生期マウス内耳発生におけるAktの活性化とPTENの発現について2008

    • Author(s)
      村田潤子、西池季隆、堀井新、土井勝美
    • Organizer
      第18回日本耳科学会総会・学術講演会
    • Place of Presentation
      神戸
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス内耳発生におけるAktの活性化とPTENの発現について2008

    • Author(s)
      村田 潤子, 他
    • Organizer
      第1 8回日本耳科学会総会・学術講演会
    • Place of Presentation
      神戸、兵庫県
    • Related Report
      2008 Annual Research Report
  • [Book] Notch Signaling in Embryology and Cancer(Notch Signaling and the Developing Inner Ear)(edited by Jorg Reichrath and Sandra Reichrath)2001

    • Author(s)
      Junko Murata, Katsuhisa Ikeda, Hideyuki Okano
    • Publisher
      Landes Bioscience and Springer Science+Business Media
    • Related Report
      2010 Annual Research Report
  • [Book] Landes Bioscience and Springer Science and Business Media 2011 in NCBI Bookshelf(edited by Jorg Reichrath and Sandra Reichrath)('Notch Signaling and the Developing Inner Ear' in 'Notch Signaling in Embryology and Cancer')

    • Author(s)
      Junko Murata, Katsuhisa Ikeda, Hideyuki Okano
    • Related Report
      2010 Final Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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