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Genetic manipulation of odorant receptor class choice and olfactory behaivor

Research Project

Project/Area Number 19H03264
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionTokyo Institute of Technology

Principal Investigator

HIROTA JUNJI  東京工業大学, 生命理工学院, 教授 (60405339)

Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2022: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords嗅覚 / 嗅覚受容体 / 遺伝子発現 / 転写因子 / 細胞分化 / 嗅覚行動 / 嗅神経細胞 / 神経分化 / 神経細胞分化
Outline of Research at the Start

嗅神経細胞は、その分化過程においてClass I型かClass II型かの運命選択をし、その運命決定に従い対応するクラスの嗅覚受容体をを発現する。しかしながら嗅神経細胞の二型性の機能分化の分子機構の全容とその生理的意義は明らかになっていない。これまでの研究で申請者は転写因子Bcl11bがこの二者択一的運命選択を制御していることを明らかにした。本研究課題では、ORクラス選択におけるBcl11bの機能発現機序の全容を解明する。さらにORクラス選択の遺伝学的制御が嗅覚神経回路形成と嗅覚行動に及ぼす影響を明らかにし、ORクラス選択と嗅覚行動を結ぶ分子神経基盤を明らかにする。

Outline of Final Research Achievements

Individual olfactory sensory neurons (OSNs) express a single odorant receptor (OR) gene from the class I or class II repertoires in mice. The mechanisms that regulate OR class choice in OSNs remain unknown. We show that the transcription factor Bcl11b determines the OR class to be expressed in OSNs. Both loss- and gain-of-function analyses demonstrate that class I is a default fate of OSNs and that Bcl11b dictates a class II OR choice by suppressing the effect of the J-element, a class I-OR enhancer. We further demonstrate that OSN-specific genetic manipulations of Bcl11b bias the OR class choice, generating mice with "class I-dominant" and "class II-dominant" noses, which display contrasting innate olfactory behaviors to two distinct aversive odorants. Overall, these findings reveal a unique transcriptional mechanism mediating 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

嗅覚受容体(OR)遺伝子の同定から四半世紀以上が経過し、その間のゲノム解析の進展によって脊椎動物のOR遺伝子レパートリーが、「魚類から哺乳類に共通の」クラス1と「陸生動物特異的な」クラス2に分類されることがわかった。しかし嗅神経細胞がどのように発現する嗅覚受容体のクラスを決定するのかは未解決のままであった。本研究は、長年の学術上の未解決問題を解明しただけでなく、魚類から哺乳動物の共通に存在するクラス1が嗅覚受容体の初期設定であること実験的に初めて証明したものであり、嗅覚の陸生適応メカニズムを新たに提唱するなど、学術的意義は極めて高い。

Report

(5 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (28 results)

All 2024 2023 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Book (1 results) Remarks (1 results)

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

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] Monell Chemical Senses Center(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Monell Chemical Senses Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Monel Chemical Senses Center(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Molecular mechanisms of differentiation and class choice of olfactory sensory neurons2024

    • Author(s)
      Hirota Junji
    • Journal Title

      genesis

      Volume: 62 Issue: 2

    • DOI

      10.1002/dvg.23587

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bcl11b is required for proper odorant receptor expression in the mouse septal organ2021

    • Author(s)
      Enomoto Takayuki、Wakui Koji、Hirota Junji
    • Journal Title

      Cell and Tissue Research

      Volume: 384 Issue: 3 Pages: 643-653

    • DOI

      10.1007/s00441-021-03444-5

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A class I odorant receptor enhancer shares a functional motif with class II enhancers2021

    • Author(s)
      Iwata Tetsuo、Tomeoka Satoshi、Hirota Junji
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 510-510

    • DOI

      10.1038/s41598-020-79980-x

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of Eya1 in mouse taste buds2021

    • Author(s)
      Ohmoto M, Kitamoto S, Hirota J
    • Journal Title

      Cell Tissue Res

      Volume: 383 Issue: 3 Pages: 979-986

    • DOI

      10.1007/s00441-020-03311-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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
  • [Presentation] Molecular mechanism of class I odorant receptor gene expression.2023

    • Author(s)
      Tetsuo Iwata, Sirapop Nithiuthai, Satoshi Tomeoka, Junji Hirota
    • Organizer
      The 19th Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impaired pheromone perception and abnormal sexual behavior in ancV1R deficient female mice2023

    • Author(s)
      Hiro Kondo, Tetsuo Iwata, Riseru Koshiishi, Hikoyu Suzuki, Ken Murata, Kazushige Touhara, Masato NIkaido, Junji Hirota
    • Organizer
      The 20th Symposium on Molecular and Neural Mechanisms of Taste and Olfactory Perception
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 嗅覚受容体クラス選択の分子機構2023

    • Author(s)
      廣田順二
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 嗅覚受容体遺伝子発現におけるSsbp2の機能解明2023

    • Author(s)
      町田夏芽、白川大地、小林千鶴、福嶋俊明、岩田哲郎、廣田順二
    • Organizer
      日本味と匂学会第57回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒトiPS細胞の分化誘導による嗅神経幹細胞の作製2023

    • Author(s)
      満留隼人、白木伸明、岩田哲郎、廣田順二
    • Organizer
      日本味と匂学会第57回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 新規鋤鼻受容体候補分子ancV1Rの雌性行動における重要性2023

    • Author(s)
      近藤 宏、岩田哲郎、鈴木彦有、村田健、東原和成、二階堂雅人、廣田順二
    • Organizer
      日本味と匂学会第57回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Class I嗅覚受容体遺伝子クラスター部分欠失マウスの解析2023

    • Author(s)
      岩田哲郎、Nithiutahi Sirapop、廣田順二
    • Organizer
      日本味と匂学会第57回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 嗅覚受容体遺伝子発現におけるSsbp2の機能解明2022

    • Author(s)
      町田夏芽、白川大地、小林千鶴、福嶋俊明、岩田哲郎、廣田順二
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 嗅神経発生最初期ニューロンの発生分化機構の解明2022

    • Author(s)
      内田樹菜、岩田哲郎、廣田順二
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Molecular mechanisms underlying super-long-range gene regulation of a class I odorant receptor enhancer2022

    • Author(s)
      Sirapop Nithiuthai, Tetsuo Iwata, Junji Hirot
    • Organizer
      第45回分子生物学会年会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 嗅覚受容体のクラス選択と嗅覚行動2020

    • Author(s)
      廣田順二
    • Organizer
      日本味と匂学会第54回大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 広範な脊椎動物に保存される新規V1R遺伝子ancV1Rの機能解析2020

    • Author(s)
      近藤宏、岩田哲郎、村田健、鈴木彦有、東原和成、二階堂雅人、廣田順二
    • Organizer
      日本味と匂学会第54回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 味細胞に発現する転写因子の探2020

    • Author(s)
      北本颯希、應本真、廣田順二
    • Organizer
      日本味と匂学会第54回大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Mechanism of odorant receptor class choice in mice2019

    • Author(s)
      Hirota, J.
    • Organizer
      Association for Chemoreception Sciences Annual Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [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、榎本孝幸、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)
      Enomoto T, Nishida H, Iwata T, Fujita A, Nakayama K, Kashiwagi T, Hatanaka Y, Kondo H, Kajitani R, Itoh T, Ohmoto M, Matsumoto I, Hirota J.
    • Organizer
      The 48th Naito Conference on Integrated Sensory Sciences - Pain , Itch, Smell and Taste.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Book] においのセンシング、分析とその可視化、数値 第1章3節「嗅覚受容体のクラス選択と遺伝子発現機構の分子メカニズム」2020

    • Author(s)
      共著(廣田順二)
    • Total Pages
      543
    • Publisher
      技術情報協会
    • Related Report
      2020 Annual Research Report
  • [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 - 遺伝子制御で匂いの感じ方が大きく変化

    • URL

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

    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2025-01-30  

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