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Molecular mechanism of odorant receptor class choice in mice

Research Project

Project/Area Number 16K07366
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionTokyo Institute of Technology

Principal Investigator

Hirota Junji  東京工業大学, バイオ研究基盤支援総合センター, 准教授 (60405339)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords嗅覚 / 嗅覚受容体 / 嗅神経細胞 / 神経分化 / 遺伝子発現 / 転写因子 / 転写調節配列 / 運命決定 / 神経科学 / 細胞 / 遺伝子
Outline of Final Research Achievements

Odorant receptors are classified into two classes: class I (aquatic), which is common in vertebrates from fish to mammals, and class II (terrestrial), which is specific to terrestrial animals. Thus, two different types of olfactory sensory neurons are produced in the nose, depending on the type of odorant receptor they express, but the mechanism has remained unknown. In this study, we, for the first time, identify the transcription factor Bcl11b as a critical regulator that determines the OR class to be expressed in OSNs. We further demonstrate that OSN-specific genetic manipulations of Bcl11b bias the OR class choice, generating mice with “class Idominant”and “class II-dominant” noses, which display contrasting innate olfactory behaviorsto two distinct aversive odorants. Overall, these findings reveal a unique transcriptional mechanism that serves as a binary switch for OR class choice that is crucial to both the anatomical and functional organization of the olfactory system.

Academic Significance and Societal Importance of the Research Achievements

ゲノム上最大の遺伝子ファミリーを形成する嗅覚受容体は大きく2つのクラスに分類されることが知られていた。嗅覚受容体の発見以来、四半世紀以上未解明であった嗅覚受容体のクラス選択の分子メカニズムを明らかにした本研究成果の学術的価値は高いと言える。また末梢神経である嗅神経細胞のクラス選択を変えるだけでマウスが感じる匂いの世界と嗅覚行動は大きく変化した結果は興味深く、今後、嗅覚受容体クラス選択と動物の嗅覚行動を繋ぐ神経基盤が解明できるものと期待される。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (47 results)

All 2020 2019 2018 2017 2016 Other

All Int'l Joint Research (5 results) Journal Article (6 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (30 results) (of which Int'l Joint Research: 10 results,  Invited: 5 results) Remarks (6 results)

  • [Int'l Joint Research] Monel Chemical Senses Center(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Monell Chemical Senses Center(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Monell Chemical Senses Center(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] Monell Chemical Senses Center(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Bcl11b controls odorant receptor class choice in mice2019

    • Author(s)
      Enomoto Takayuki、Nishida Hidefumi、Iwata Tetsuo、Fujita Akito、Nakayama Kanako、Kashiwagi Takahiro、Hatanaka Yasue、Kondo Hiro、Kajitani Rei、Itoh Takehiko、Ohmoto Makoto、Matsumoto Ichiro、Hirota Junji
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 296-296

    • DOI

      10.1038/s42003-019-0536-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ゲノム最大級の巨大遺伝子クラスターを制御するゲノム領域の発見2018

    • Author(s)
      岩田哲郎、廣田順二
    • Journal Title

      バイオサイエンスとインダストリー

      Volume: 76(3) Pages: 232-233

    • Related Report
      2018 Research-status Report
  • [Journal Article] 匂い受容体遺伝子の新たな発現制御領域の発見2018

    • Author(s)
      岩田哲郎、廣田順二
    • Journal Title

      アロマリサーチ

      Volume: 19(2) Pages: 32-33

    • Related Report
      2018 Research-status Report
  • [Journal Article] A long-range cis-regulatory element for class I odorant receptor genes2017

    • Author(s)
      Iwata Tetsuo、Niimura Yoshihito、Kobayashi Chizuru、Shirakawa Daichi、Suzuki Hikoyu、Enomoto Takayuki、Touhara Kazushige、Yoshihara Yoshihiro、Hirota Junji
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1-12

    • DOI

      10.1038/s41467-017-00870-4

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Skn-1a/Pou2f3 functions as a master regulator to generate Trpm5-expressing chemosensory cells in mice2017

    • Author(s)
      Yamashita Junpei、Ohmoto Makoto、Yamaguchi Tatsuya、Matsumoto Ichiro、Hirota Junji
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 12 Pages: 1-14

    • DOI

      10.1371/journal.pone.0189340

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bcl11b/Ctip2 is required for development of lingual papillae in mice2016

    • Author(s)
      Yugo Nishiguchi, Makoto Ohmoto, Jun Koki, Takayuki Enomoto, Ryo Kominami, Ichiro Matsumoto, Junji Hirota
    • Journal Title

      Developmental Biology

      Volume: 416 Issue: 1 Pages: 98-110

    • DOI

      10.1016/j.ydbio.2016.06.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Odorant receptor class choice and olfactory behaviors2020

    • Author(s)
      Junji Hirota
    • Organizer
      International Symposium on “Environmental Response Mechanisms in Plants and Animals”
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Molecular mechanism of odorant receptor class choice in mice2019

    • Author(s)
      Junji Hirota
    • Organizer
      Association for Chemoreception Sciences Annual Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Class I嗅覚受容体遺伝子の発現制御機構2019

    • Author(s)
      岩田哲郎、廣田順二
    • Organizer
      日本味と匂い学会第53回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 嗅覚受容体の遺伝子発現制御機構2019

    • Author(s)
      廣田順二
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Mechanism of odorant receptor class choice in mice2019

    • Author(s)
      Takayuki Enomoto, Hidefumi Nishida, Tetsuo Iwata, Akito Fujita, Kanako Nakayama, Takahiro Kashiwagi, Yasue Hatanaka, Hiro Kondo, Rei Kajitani, Takehiko Itoh, Makoto Ohmoto, Ichiro Matsumoto, Junji Hirota
    • Organizer
      The 48th Naito Conference on Integrated Sensory Sciences - Pain , Itch, Smell and Taste.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 香りを感知する嗅神経細胞の多様性創出の分子機構2019

    • Author(s)
      廣田順二
    • Organizer
      第11回香りと味に関する産学フォーラム(日本バーチャルリアリティ学会)
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Class I嗅覚受容体遺伝子転写調節領域の機能解析2019

    • Author(s)
      岩田哲郎、留岡諭志、廣田順二
    • Organizer
      第6回ケモビ研究会
    • Related Report
      2018 Research-status Report
  • [Presentation] Molecular mechanism of odorant receptor class choice in mice2018

    • Author(s)
      Junji Hirota
    • Organizer
      The 17th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 嗅覚受容体遺伝子発現における転写因子Ldb1の機能解析2018

    • Author(s)
      猪爪舞花、岩田哲郎、Saiku Daniel、齋藤真人、飯塚遥香、小澤悠太、永嶌鮎美、廣田順二
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 転写因子Bcl11bによる嗅神経細胞の二者択一的運命決定の制御機構の解明2018

    • Author(s)
      柏木貴裕、榎本孝幸、岩田哲郎、廣田順二
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Class I 嗅覚受容体遺伝子の転写調節領域の機能解析2018

    • Author(s)
      留岡諭志、岩田哲郎、廣田順二 日本味と匂学会第52回大会
    • Organizer
      日本味と匂学会第52回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 嗅覚受容体巨大遺伝子クラスターを制御する長距離シスエレメント2018

    • Author(s)
      岩田哲郎、新村芳人、小林千鶴、白川大地、鈴木彦有、榎本孝幸、東原和成、吉原良浩、廣田順
    • Organizer
      日本遺伝学会第90回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] An extraordinary long-range cis-regulatory element for class I odorant receptor genes2018

    • Author(s)
      Tetsuo Iwata, Yoshihito Niimura,, Chizuru Kobayashi, Daichi Shirakawa, Hikoyu Suzuki, Takayuki Enomoto, Kazushige Touhara, Yoshihiro Yoshihara Junji Hirota
    • Organizer
      ゲノム編集学会第3回大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Class II嗅覚受容体遺伝子発現制御2018

    • Author(s)
      廣田順二
    • Organizer
      第5回ケモビ研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Class II嗅覚受容体発現におけるLhx2転写因子複合体の機能2018

    • Author(s)
      猪爪舞花、廣田順二
    • Organizer
      第5回ケモビ研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Class I嗅覚受容体遺伝子発現制御2018

    • Author(s)
      岩田哲郎、廣田順二
    • Organizer
      第5回ケモビ研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Class I嗅覚受容体遺伝子の長距離シスエレメントの同定2018

    • Author(s)
      留岡諭志、岩田哲郎、廣田順二
    • Organizer
      第5回ケモビ研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 6)Trpm5陽性化学感覚細胞における転写因子Skn-1aの機能2018

    • Author(s)
      山下純平、廣田順二
    • Organizer
      第5回ケモビ研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] 嗅覚受容体遺伝子発現制御と陸棲適応2017

    • Author(s)
      岩田哲郎、廣田順二
    • Organizer
      第4回ケモビ研究会
    • Place of Presentation
      雫石
    • Year and Date
      2017-02-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 嗅神経細胞分化の遺伝学的操作による本能的な忌避行動の制御2017

    • Author(s)
      榎本孝幸、廣田順二
    • Organizer
      第4回ケモビ研究会
    • Place of Presentation
      雫石
    • Year and Date
      2017-02-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Bcl11bは2種類の嗅神経細胞の運命選択を支配する2017

    • Author(s)
      榎本孝幸、西田秀史、岩田哲郎中山叶子、藤田暁登、柏木貴裕、畠中靖恵、梶谷嶺、伊藤武彦、應本真、松本一朗、廣田順二
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 白川大地、小林千鶴、岩田哲郎、廣田順二2017

    • Author(s)
      嗅覚受容体遺伝子発現における転写因子Ssbp2の機能解析
    • Organizer
      日本味と匂学会第51回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 山下純平、應本真、山口達也、松本一朗、廣田順二2017

    • Author(s)
      Trpm5陽性化学感覚細胞における転写因子Pou2f3/Skn-1aの機能解析
    • Organizer
      日本味と匂学会第51回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 岩田哲郎、新村芳人、小林千鶴、白川大地、鈴木彦有、榎本孝幸、東原和成、吉原良浩、廣田順二2017

    • Author(s)
      Class I嗅覚受容体遺伝子の長距離シスエレメントの同定
    • Organizer
      日本味と匂学会第51回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Skn-1a/Pou2f3 functions as a master regulator to genarate Trpm5-expressing chemosensory cells in mice2017

    • Author(s)
      Junpei Yamashita, Makoto Ohmoto, Tatsuya Yamaguchi, Ichiro Matsumoto, Junji Hirota
    • Organizer
      16th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Bcl11b Governs the Binary Fate of Olfactory Sensory Neurons2016

    • Author(s)
      Takayuki Enomoto, Hidefumi Nishida, Tetsuo Iwata, Kanako Nakayama, Akito Fujita, Takahiro Kashiwagi, Rei Kajitani, Takehiko Ito, Makoto Ohmoto, Ichiro Matsumoto, and Junji Hirota
    • Organizer
      The 14th International Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Place of Presentation
      Fukuoka
    • Year and Date
      2016-12-03
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression analysis of Bcl11b in Xenopus tropicalis olfactory epithelium2016

    • Author(s)
      Kanako Nakayama, Hikoyu Suzuki, Masato Nikaido, Takayuki Enomoto, Junji Hirota
    • Organizer
      The 17th International Symposium on Olfaction and Taste
    • Place of Presentation
      Yokohama
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Studies on the cis-element for mouse class I odorant receptor genes using the Bacillus subtilis genome vector2016

    • Author(s)
      Tetsuo Iwata, Shinya Kaneko, Takafumi Ogawa, Chizuru Kobayashi, Yuh Shiwa, Takayuki Enomoto, Hirofumi Yoshikawa, Junji Hirota
    • Organizer
      The 17th International Symposium on Olfaction and Taste
    • Place of Presentation
      Yokohama
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional analysis of CTCF in odorant receptor gene expression in mice2016

    • Author(s)
      Chizuru Kobayashi, Tetsuo Iwata, Niles Galjart, Junji Hirota
    • Organizer
      The 17th International Symposium on Olfaction and Taste
    • Place of Presentation
      Yokohama
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The fate choice of olfactory sensory neurons in mice2016

    • Author(s)
      Junji Hirota
    • Organizer
      “Olfaction: from Chemosensory Signals to the Brain”, ISOT2016 Satellite Meeting
    • Place of Presentation
      Tokyo
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Remarks] 鼻の中でタイプの異なる匂いセンサーができる仕組みを解明

    • URL

      https://www.titech.ac.jp/news/2019/044993.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 超巨大遺伝子群を制御するゲノム領域を発見

    • URL

      https://www.titech.ac.jp/news/2017/039272.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 超巨大遺伝子群を制御するゲノム領域を発見 ―匂い受容体の遺伝子進化の謎の解明へ―

    • URL

      https://www.titech.ac.jp/news/2017/039272.html

    • Related Report
      2017 Research-status Report
  • [Remarks] Pioneering Discovery of an Odor-detecting Rec...

    • URL

      https://www.titech.ac.jp/english/news/2017/039367.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 体を外敵から守る化学感覚細胞のマスター因子を同定―舌だけではない!全身の味細胞の機能解明へ―

    • URL

      https://www.titech.ac.jp/news/2017/039980.html

    • Related Report
      2017 Research-status Report
  • [Remarks] A whole-body approach to understanding chemo...

    • URL

      https://www.titech.ac.jp/english/news/2017/040087.html

    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2022-02-21  

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