Molecular mechanism of odorant receptor class choice in mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K07366
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Tokyo 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
• Keywords: 嗅覚 / 嗅覚受容体 / 嗅神経細胞 / 神経分化 / 遺伝子発現

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.

Free Research Field

分子神経科学

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。