Updated on 2025/09/12

写真a

 
HIROTA JUNJI
 
Organization
School of Life Science and Technology Professor
Title
Professor
Homepage
http://www.hirota.bio.titech.ac.jp/
External link

News & Topics

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Degree

  • 工学博士 ( 1995   東京工業大学 )

Research Interests

  • 分子神経科学、ゲノム工学

  • 嗅神経細胞

  • 化学感覚

  • ゲノム工学

  • マウス発生工学

  • 人工ゲノムベクター

  • 神経分化

  • 神経発生

  • 遺伝子発現

  • 嗅覚受容体

  • 嗅覚

Research Areas

  • Life Science / Developmental biology

  • Life Science / Neuroscience-general

  • Life Science / Genome biology  / Genome Engineering

Education

  • Tokyo Institute of Technology   Bioscience and Biotechnology

    1992.4 - 1995.9

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    Country： Japan

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  • 東京大学 医学系研究科 第二基礎医学専攻 大学院特別研究学生

    1993.4 - 1995.9

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Research History

  • Institute of Science Tokyo   Vice President for Biomedical Engineering, Vice President for Integrated Research and Inovation

    2024.10

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    Country：Japan

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  • Institute of Science Tokyo   School of Life Science and Technology   Professor

    2024.10

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    Country：Japan

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  • Institute of Science Tokyo   Bioscience Center   Director

    2024.10

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    Country：Japan

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  • Tokyo Institute of Technology   Center for Integrative Biosciences   Director

    2023.4 - 2024.9

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  • Tokyo Institute of Technology   School of Life Science and Technology   Professor

    2021.6 - 2024.9

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  • Tokyo Institute of Technology   School of Life Science and Technology   Associate Professor

    2020.4 - 2021.5

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  • Tokyo Institute of Technology   Center for Biological Resources and Informatics   Associate Professor

    2008.4 - 2020.3

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  • 大阪府立大学 大学院理学研究科 准教授

    2005.4 - 2008.3

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  • The Rockefeller University, 博士研究員（Prof. P. Mombaerts)

    2000 - 2005

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  • Human Frontier Science Program, Long-Term Fellow

    2000 - 2003

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  • The University of Tokyo   The Institute of Medical Science

    1995 - 2000

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  • 科学技術振興事業団 ERATO御子柴細胞制御プロジェクト 研究員

    1995 - 2000

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Professional Memberships

Committee Memberships

  • The Japanese Association for the Study of Taste and Smell   Steering committee member  

    2024.4   

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    Committee type：Academic society

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  • The Japanese Association for the Study of Taste and Smell   Steering committee member, General manager  

    2021.4 - 2024.3   

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    Committee type：Academic society

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  • 日本味と匂学会   日本味と匂学会誌編集員  

    2009.4 - 2021.3   

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    Committee type：Academic society

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  • 日本味と匂学会   評議員  

    2007   

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    Committee type：Academic society

    日本味と匂学会

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Papers

  • Impaired pheromone detection and abnormal sexual behavior in female mice deficient for ancV1R Reviewed

    Hiro Kondo, Tetsuo Iwata, Koji Sato, Riseru Koshiishi, Hikoyu Suzuki, Ken Murata, Marc Spehr, Kazushige Touhara, Masato Nikaido, Junji Hirota

    Current Biology   35   1 - 15   2024.11

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.cub.2024.10.077

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  • Molecular mechanisms of differentiation and class choice of olfactory sensory neurons Invited Reviewed

    Junji Hirota

    Genesis   62 ( 2 )   2024.3

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    Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

    Summary

    The sense of smell is intricately linked to essential animal behaviors necessary for individual survival and species preservation. During vertebrate evolution, odorant receptors (ORs), responsible for detecting odor molecules, have evolved to adapt to changing environments, transitioning from aquatic to terrestrial habitats and accommodating increasing complex chemical environments. These evolutionary pressures have given rise to the largest gene family in vertebrate genomes. Vertebrate ORs are phylogenetically divided into two major classes; class I and class II. Class I OR genes, initially identified in fish and frog, have persisted across vertebrate species. On the other hand, class II OR genes are unique to terrestrial animals, accounting for ~90% of mammalian OR genes. In mice, each olfactory sensory neuron (OSN) expresses a single functional allele of a single OR gene from either the class I or class II OR repertoire. This one neuron‐one receptor rule is established through two sequential steps: specification of OR class and subsequent exclusive OR expression from the corresponding OR class. Consequently, OSNs acquire diverse neuronal identities during the process of OSN differentiation, enabling animals to detect a wide array of odor molecules. This review provides an overview of the OSN differentiation process through which OSN diversity is achieved, primarily using the mouse as a model animal.

    DOI： 10.1002/dvg.23587

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  • 5, 6, 11-trideoxy tetrodotoxin attracts tiger puffer Takifugu rubripes Reviewed

    Kairi Miyazaki, Rei Suo, Shiro Itoi, Junji Hirota, Masaatsu Adachi, Tadachika Miyasaka, Toshio Nishikawa, Takehiko Yokoyama, Shigeru Sato, Kentaro Takada

    Toxicon   237   107539 - 107539   2024.1

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    Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.toxicon.2023.107539

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  • Maintenance and turnover of Sox2+ adult stem cells in the gustatory epithelium Reviewed

    Makoto Ohmoto, Shugo Nakamura, Hong Wang, Peihua Jiang, Junji Hirota, Ichiro Matsumoto

    PLOS ONE   17 ( 9 )   e0267683 - e0267683   2022.9

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

    Continuous turnover of taste bud cells in the oral cavity underlies the homeostasis of taste tissues. Previous studies have demonstrated that Sox2+stem cells give rise to all types of epithelial cells including taste bud cells and non-gustatory epithelial cells in the oral epithelium, and Sox2 is required for generating taste bud cells. Here, we show the dynamism of single stem cells through multicolor lineage tracing analyses inSox2-CreERT2;Rosa26-Confettimice. In the non-gustatory epithelium, unicolored areas populated by a cluster of cells expressing the same fluorescent protein grew over time, while epithelial cells were randomly labeled with multiple fluorescent proteins by short-term tracing. Similar phenomena were observed in gustatory epithelia. These results suggest that the Sox2+stem cell population is maintained by balancing the increase of certain stem cells with the reduction of the others. In the gustatory epithelia, many single taste buds contained cells labeled with different fluorescent proteins, indicating that a single taste bud is composed of cells derived from multiple Sox2+stem cells. Our results reveal the characteristics of Sox2+stem cells underlying the turnover of taste bud cells and the homeostasis of taste tissues.

    DOI： 10.1371/journal.pone.0267683

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  • Bcl11b is required for proper odorant receptor expression in the mouse septal organ. Reviewed International journal

    Takayuki Enomoto, Koji Wakui, Junji Hirota

    Cell and Tissue Research   2021.3

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Individual olfactory sensory neurons (OSNs) in the mouse main olfactory epithelium express a single odorant receptor (OR) gene from the repertoire of either class I or class II ORs. The transcription factor Bcl11b determines the OR class to be expressed in OSNs. The septal organ (SO), a small neuroepithelium located at the ventral base of the nasal septum, is considered as an olfactory subsystem because it expresses a specific subset of ORs. However, the mechanisms underlying the generation and differentiation of SO-OSN remain unknown. In the present study, we show that the generation and differentiation of SO-OSN employ the same genetic pathway as in the OSN lineage, which is initiated by the neuronal fate determinant factor Ascl1. Additionally, the key role of Bcl11b in the SO is demonstrated by the abnormal phenotypes of Bcl11b-deficient mice: significant reduction in the expression of OR genes and in the number of mature SO-OSNs. Although SO-OSNs are specified to express a subset of class II OR genes in wild-type mice, the Bcl11b deletion led to the expression of class I OR genes, while the expression of class II OR genes was significantly decreased, with one exception of Olfr15. These results indicate that Bcl11b is necessary for proper OR expression in SO-OSNs.

    DOI： 10.1007/s00441-021-03444-5

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  • Expression of Eya1 in mouse taste buds. Reviewed International journal

    Makoto Ohmoto, Satsuki Kitamoto, Junji Hirota

    Cell and Tissue Research   383 ( 3 )   979 - 986   2021.3

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Taste substances are detected by taste receptor cells in the taste buds in the oral epithelium. Individual taste receptor cells contribute to evoking one of the five taste qualities: sweet, umami, bitter, sour, and salty (sodium). They are continuously replaced every few weeks by new ones generated from local epithelial stem cells. A POU transcription factor, Pou2f3 (also known as Skn-1a), regulates the generation and differentiation of sweet, umami, and bitter cells. However, the molecular mechanisms underlying terminal differentiation into these Pou2f3-dependent taste receptor cells remain unknown. To identify the candidate molecules that regulate the differentiation of these taste receptor cells, we searched for taste receptor type-specific transcription factors using RNA-sequence data of sweet and bitter cells. No transcription factor gene showing higher expression in sweet cells than in bitter cells was found. Eyes absent 1 (Eya1) was identified as the only transcription factor gene showing higher expression in bitter cells than in sweet cells. In situ hybridization revealed that Eya1 was predominantly expressed in bitter cells and also in the putative immature/differentiating taste bud cells in circumvallate and fungiform papillae and soft palate. Eya1 is a candidate molecule that regulates the generation and differentiation of bitter cells.

    DOI： 10.1007/s00441-020-03311-9

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  • A class I odorant receptor enhancer shares a functional motif with class II enhancers. Reviewed International journal

    Tetsuo Iwata, Satoshi Tomeoka, Junji Hirota

    Scientific Reports   11 ( 1 )   510 - 510   2021.1

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    In the mouse, 129 functional class I odorant receptor (OR) genes reside in a ~ 3 megabase huge gene cluster on chromosome 7. The J element, a long-range cis-regulatory element governs the singular expression of class I OR genes by exerting its effect over the whole cluster. To elucidate the molecular mechanisms underlying class I-specific enhancer activity of the J element, we analyzed the J element sequence to determine the functional region and essential motif. The 430-bp core J element, that is highly conserved in mammalian species from the platypus to humans, contains a class I-specific conserved motif of AAACTTTTC, multiple homeodomain sites, and a neighboring O/E-like site, as in class II OR-enhancers. A series of transgenic reporter assays demonstrated that the class I-specific motif is not essential, but the 330-bp core J-H/O containing the homeodomain and O/E-like sites is necessary and sufficient for class I-specific enhancer activity. Further motif analysis revealed that one of homeodomain sequence is the Greek Islands composite motif of the adjacent homeodomain and O/E-like sequences, and mutations in the composite motif abolished or severely reduced class I-enhancer activity. Our results demonstrate that class I and class II enhancers share a functional motif for their enhancer activity.

    DOI： 10.1038/s41598-020-79980-x

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  • SOX2 regulates homeostasis of taste bud cells and lingual epithelial cells in posterior tongue Reviewed International journal

    Makoto Ohmoto, Weiwei Lei, Junpei Yamashita, Junji Hirota, Peihua Jiang, Ichiro Matsumoto

    PLOS ONE   15 ( 10 )   e0240848 - e0240848   2020.10

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Public Library of Science (PLoS)  

    Taste bud cells arise from local epithelial stem cells in the oral cavity and are continuously replaced by newborn cells throughout an animal's life. However, little is known about the molecular and cellular mechanisms of taste cell turnover. Recently, it has been demonstrated that SOX2, a transcription factor expressed in epithelial stem/progenitor cells of the oral cavity, regulates turnover of anterior tongue epithelium including gustatory and non-gustatory papillae. Yet, the role of SOX2 in regulating taste cell turnover in the posterior tongue is unclear. Prompted by the fact that there are regional differences in the cellular and molecular composition of taste buds and stem/progenitor cells in the anterior and posterior portions of tongue, which are derived from distinct embryonic origins, we set out to determine the role of SOX2 in epithelial tissue homeostasis in the posterior tongue. Here we report the differential requirement of SOX2 in the stem/progenitor cells for the normal turnover of lingual epithelial cells in the posterior tongue. Sox2 deletion in the stem/progenitor cells neither induced active caspase 3-mediated apoptotic cell death nor altered stem/progenitor cell population in the posterior tongue. Nevertheless, morphology and molecular feature of non-gustatory epithelial cells were impaired in the circumvallate papilla but not in the filiform papillae. Remarkably, taste buds became thinner, collapsed, and undetectable over time. Lineage tracing of Sox2-deleted stem/progenitor cells demonstrated an almost complete lack of newly generated basal precursor cells in the taste buds, suggesting mechanistically that Sox2 is involved in determining stem/progenitor cells to differentiate to gustatory lineage cells. Together, these results demonstrate that SOX2 plays key roles in regulating epithelial tissue homeostasis in the posterior tongue, similar but not identical to its function in the anterior tongue.

    DOI： 10.1371/journal.pone.0240848

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  • Bcl11b controls odorant receptor class choice in mice Reviewed International journal

    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

    Communications Biology   2 ( 1 )   296 - 296   2019.12

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

    Each olfactory sensory neuron (OSN) expresses a single odorant receptor (OR) gene from the class I or class II repertoire in mice. The mechanisms that regulate OR class choice in OSNs remain unknown. Here, 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.

    DOI： 10.1038/s42003-019-0536-x

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    Other Link： http://www.nature.com/articles/s42003-019-0536-x

  • A Single Pheromone Receptor Gene Conserved across 400 My of Vertebrate Evolution. Reviewed International journal

    Hikoyu Suzuki, Hidefumi Nishida, Hiro Kondo, Ryota Yoda, Tetsuo Iwata, Kanako Nakayama, Takayuki Enomoto, Jiaqi Wu, Keiko Moriya-Ito, Masao Miyazaki, Yoshihiro Wakabayashi, Takushi Kishida, Masataka Okabe, Yutaka Suzuki, Takehiko Ito, Junji Hirota, Masato Nikaido

    Molecular Biology and Evolution   35 ( 12 )   2928 - 2939   2018.12

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    Pheromones are crucial for eliciting social and sexual behaviors in diverse animal species. The vomeronasal receptor type-1 (V1R) genes, encoding members of a pheromone receptor family, are highly variable in number and repertoire among mammals due to extensive gene gain and loss. Here, we report a novel pheromone receptor gene belonging to the V1R family, named ancient V1R (ancV1R), which is shared among most Osteichthyes (bony vertebrates) from the basal lineage of ray-finned fishes to mammals. Phylogenetic and syntenic analyses of ancV1R using 115 vertebrate genomes revealed that it represents an orthologous gene conserved for >400 My of vertebrate evolution. Interestingly, the loss of ancV1R in some tetrapods is coincident with the degeneration of the vomeronasal organ in higher primates, cetaceans, and some reptiles including birds and crocodilians. In addition, ancV1R is expressed in most mature vomeronasal sensory neurons in contrast with canonical V1Rs, which are sparsely expressed in a manner that is consistent with the "one neuron-one receptor" rule. Our results imply that a previously undescribed V1R gene inherited from an ancient Silurian ancestor may have played an important functional role in the evolution of vertebrate vomeronasal organ.

    DOI： 10.1093/molbev/msy186

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  • Skn-1a/Pou2f3 functions as a master regulator to generate Trpm5-expressing chemosensory cells in mice Reviewed

    Junpei Yamashita, Makoto Ohmoto, Tatsuya Yamaguchi, Ichiro Matsumoto, Junji Hirota

    PLOS ONE   12 ( 12 )   e0189340 - e0189340   2017.12

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    DOI： 10.1371/journal.pone.0189340

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  • A long-range cis-regulatory element for class I odorant receptor genes Reviewed International journal

    Tetsuo Iwata, Yoshihito Niimura, Chizuru Kobayashi, Daichi Shirakawa, Hikoyu Suzuki, Takayuki Enomoto, Kazushige Touhara, Yoshihiro Yoshihara, Junji Hirota

    Nature Communications   8 ( 1 )   885 - 885   2017.12

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-017-00870-4

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    Other Link： http://www.nature.com/articles/s41467-017-00870-4

  • Genetic Lineage Tracing in Taste Tissues Using Sox2-CreERT2 Strain Reviewed

    Makoto Ohmoto, Wenwen Ren, Yugo Nishiguchi, Junji Hirota, Peihua Jiang, Ichiro Matsumoto

    CHEMICAL SENSES   42 ( 7 )   547 - 552   2017.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1093/chemse/bjx032

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  • Bcl11b/Ctip2 is required for development of lingual papillae in mice Reviewed

    Yugo Nishiguchi, Makoto Ohmoto, Jun Koki, Takayuki Enomoto, Ryo Kominami, Ichiro Matsumoto, Junji Hirota

    DEVELOPMENTAL BIOLOGY   416 ( 1 )   98 - 110   2016.8

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.ydbio.2016.06.001

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  • An inducible recA expression Bacillus subtilis genome vector for stable manipulation of large DNA fragments Reviewed

    Takafumi Ogawa, Tetsuo Iwata, Shinya Kaneko, Mitsuhiro Itaya, Junji Hirota

    BMC GENOMICS   16   209   2015.3

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/s12864-015-1425-4

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  • Skn-1a/Pou2f3 is required for the generation of Trpm5-expressing microvillous cells in the mouse main olfactory epithelium Reviewed

    Tatsuya Yamaguchi, Junpei Yamashita, Makoto Ohmoto, Imad Aoude, Tatsuya Ogura, Wangmei Luo, Alexander A. Bachmanov, Weihong Lin, Ichiro Matsumoto, Junji Hirota

    BMC NEUROSCIENCE   15   13   2014.1

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/1471-2202-15-13

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  • Bacillus subtilis genome vector-based complete manipulation and reconstruction of genomic DNA for mouse transgenesis Reviewed

    Tetsuo Iwata, Shinya Kaneko, Yuh Shiwa, Takayuki Enomoto, Hirofumi Yoshikawa, Junji Hirota

    BMC GENOMICS   14   300   2013.5

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1186/1471-2164-14-300

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  • Pou2f3/Skn-1a is necessary for the generation or differentiation of solitary chemosensory cells in the anterior nasal cavity Reviewed

    Makoto Ohmoto, Tatsuya Yamaguchi, Junpei Yamashita, Alexander A. Bachmanov, Junji Hirota, Ichiro Matsumoto

    Bioscience, Biotechnology and Biochemistry   77 ( 10 )   2154 - 2156   2013

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1271/bbb.130454

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  • Bcl11b/Ctip2 Controls the Differentiation of Vomeronasal Sensory Neurons in Mice Reviewed

    Takayuki Enomoto, Makoto Ohmoto, Tetsuo Iwata, Ayako Uno, Masato Saitou, Tatsuya Yamaguchi, Ryo Kominami, Ichiro Matsumoto, Junji Hirota

    JOURNAL OF NEUROSCIENCE   31 ( 28 )   10159 - 10173   2011.7

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1523/JNEUROSCI.1245-11.2011

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  • Differential impact of Lhx2 deficiency on expression of class I and class II odorant receptor genes in mouse Reviewed

    Junji Hirota, Masayo Omura, Peter Mombaerts

    MOLECULAR AND CELLULAR NEUROSCIENCE   34 ( 4 )   679 - 688   2007.4

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.mcn.2007.01.014

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  • Differential impact of Lhx2 deficiency on expression of class I and class II odorant receptor genes in mouse Reviewed

    Junji Hirota, Masayo Omura, Peter Mombaerts

    NEUROSCIENCE RESEARCH   58   S218 - S218   2007

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    DOI： 10.1016/j.neures.2007.06.454

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  • The promoter of the mouse odorant receptor gene M71 Reviewed

    A Rothman, P Feinstein, J Hirota, P Mombaerts

    MOLECULAR AND CELLULAR NEUROSCIENCE   28 ( 3 )   535 - 546   2005.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.mcn.2004.11.006

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  • The LIM-homeodomain protein Lhx2 is required for complete development of mouse olfactory sensory neurons Reviewed

    J Hirota, P Mombaerts

    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA   101 ( 23 )   8751 - 8755   2004.6

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    DOI： 10.1073/pnas.0400940101

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  • Targeting a complex transcriptome: The construction of the mouse full-length cDNA encyclopedia Reviewed

    P Carninci, K Waki, T Shiraki, H Konno, K Shibata, M Itoh, K Aizawa, T Arakawa, Y Ishii, D Sasaki, H Bono, S Kondo, Y Sugahara, R Saito, N Osato, S Fukuda, K Sato, A Watahiki, T Hirozane-Kishikawa, M Nakamura, Y Shibata, A Yasunishi, N Kikuchi, A Yoshiki, M Kusakabe, S Gustincich, K Beisel, W Pavan, Aidinis, V, A Nakagawara, WA Held, H Iwata, T Kono, H Nakauchi, P Lyons, C Wells, DA Hume, M Fagiolini, TK Hensch, M Brinkmeier, S Camper, J Hirota, P Mombaerts, M Muramatsu, Y Okazaki, J Kawai, Y Hayashizaki

    GENOME RESEARCH   13 ( 6B )   1273 - 1289   2003.6

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    DOI： 10.1101/gr.1119703

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  • Carbonic anhydrase-related protein is a novel binding protein for inositol 1,4,5-trisphosphate receptor type 1 Reviewed

    J Hirota, H Ando, K Hamada, K Mikoshiba

    BIOCHEMICAL JOURNAL   372 ( 2 )   435 - 441   2003.6

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    DOI： 10.1042/BJ20030110

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  • Combinatorial coexpression of neural and immune multigene families in mouse vomeronasal sensory neurons Reviewed

    T Ishii, J Hirota, P Mombaerts

    CURRENT BIOLOGY   13 ( 5 )   394 - 400   2003.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/S0960-9822(03)00092-7

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  • Two-state conformational changes in inositol 1,4,5-trisphosphate receptor regulated by calcium Reviewed

    K Hamada, T Miyata, K Mayanagi, J Hirota, K Mikoshiba

    JOURNAL OF BIOLOGICAL CHEMISTRY   277 ( 24 )   21115 - 21118   2002.6

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    DOI： 10.1074/jbc.C200244200

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  • Inositol 1,4,5-trisphosphate receptor type 1 is a substrate for caspase-3 and is cleaved during apoptosis in a caspase-3-dependent manner Reviewed

    J Hirota, T Furuichi, K Mikoshiba

    JOURNAL OF BIOLOGICAL CHEMISTRY   274 ( 48 )   34433 - 34437   1999.11

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    DOI： 10.1074/jbc.274.48.34433

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  • Calmodulin mediates calcium-dependent inactivation of the cerebellar type 1 inositol 1,14,5-trisphosphate receptor Reviewed

    T Michikawa, J Hirota, S Kawano, M Hiraoka, M Yamada, T Furuichi, K Mikoshiba

    NEURON   23 ( 4 )   799 - 808   1999.8

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/S0896-6273(01)80037-4

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  • Calmodulin inhibits inositol 1,4,5-trisphosphate-induced calcium release through the purified and reconstituted inositol 1,4,5-trisphosphate receptor type 1 Reviewed

    J Hirota, T Michikawa, T Natsume, T Furuichi, K Mikoshiba

    FEBS LETTERS   456 ( 2 )   322 - 326   1999.8

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/S0014-5793(99)00973-4

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  • Real time analysis of interaction between inositol 1,4,5-trisphosphate receptor type I and its ligand Reviewed

    T Natsume, J Hirota, F Yoshikawa, T Furuichi, K Mikoshiba

    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS   260 ( 2 )   527 - 533   1999.7

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    DOI： 10.1006/bbrc.1999.0905

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  • T-cell-receptor signalling in inositol 1,4,5-trisphosphate receptor (IP3R) type-1-deficient mice: is IP3R type 1 essential for T-cell-receptor signalling? Reviewed

    J Hirota, M Baba, M Matsumoto, T Furuichi, K Takatsu, K Mikoshiba

    BIOCHEMICAL JOURNAL   333   615 - 619   1998.8

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  • KINETICS OF CALCIUM-RELEASE BY IMMUNOAFFINITY-PURIFIED INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR IN RECONSTITUTED LIPID VESICLES Reviewed

    J HIROTA, T MICHIKAWA, A MIYAWAKI, T FURUICHI, OKURA, I, K MIKOSHIBA

    JOURNAL OF BIOLOGICAL CHEMISTRY   270 ( 32 )   19046 - 19051   1995.8

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    DOI： 10.1074/jbc.270.32.19046

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  • ADENOPHOSTIN-MEDICATED QUANTAL CA2+ RELEASE IN THE PURIFIED AND RECONSTITUTED INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR-TYPE-1 Reviewed

    J HIROTA, T MICHIKAWA, A MIYAWAKI, M TAKAHASHI, K TANZAWA, OKURA, I, T FURUICHI, K MIKOSHIBA

    FEBS LETTERS   368 ( 2 )   248 - 252   1995.7

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    DOI： 10.1016/0014-5793(95)00659-W

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  • IP3レセプターによる情報伝達機構の解析法、細胞内膜系Ca2+チャネル実験 分子医科学実験プロトコール Reviewed

    廣田順二, 幸田和久, 宮脇敦史, 古市貞一, 御子柴克彦

    細胞工学別冊   別冊 ( 分子医科学実験プロトコール )   83 - 94   1995

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  • PREPARATION AND CHARACTERIZATION OF BISVIOLOGEN-LINKED PORPHYRIN AND BISVIOLOGEN-LINKED ZINC PORPHYRIN Reviewed

    J HIROTA, T TAKENO, OKURA, I

    JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY   77 ( 1 )   29 - 35   1994.1

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    DOI： 10.1016/1010-6030(94)80005-7

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  • Characterization of sulfonated zinc phthalocyanines as photosensitizers for photodynamic therapy Reviewed

    Takeno T, Hirota J, Kamachi T, Okura I, Sakuma Y, Nishisama T

    Lasers in the Life Sciences   6   173 - 179   1994

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  • PHOTOINDUCED INTRAMOLECULAR ELECTRON-TRANSFER IN BISVIOLOGEN-LINKED PORPHYRIN IN ACETONITRILE Reviewed

    J HIROTA, OKURA, I

    JOURNAL OF PHYSICAL CHEMISTRY   97 ( 26 )   6867 - 6870   1993.7

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    DOI： 10.1021/j100128a020

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Books

  • においのセンシング、分析とその可視化、数値化

    技術情報協会（ Role： Contributorpp.17-25 「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」）

    技術情報協会  2020.10  （ ISBN:9784861048104 ）

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  • 酵素・タンパク質をはかる・とらえる・利用する

    （ Role： Contributorpp.158-168「個体レベルで遺伝子を操作する」）

    工学図書  2009 

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  • Challenges for Neuroscience in the 21st Century, Taniguchi Symposia on Brain Sciences. (Hayaishi O, Ito M, Sano Y, Takagi H, Tsukada Y and Nakajima T, eds) No. 22

    Mikoshiba K, Furuichi T, Miyawaki A, Michikawa T, Yamamoto-Hino M, Hirota J, Tekei K, Inoue T, Kume S, Matsumoto M, Muto A（ Role： Joint author）

    Japan Scientific Societies Press, KARGER  2000.1  （ ISBN:9783805570343 ）

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  • 細胞工学別冊・分子医科学実験プロトコール

    廣田順二, 幸田和久, 宮脇敦史, 古市貞一, 御子柴克彦（ Role： Joint authorIP3レセプターによる 情報伝達機構の解析法-細胞内膜系のCa2+チャンネル実験）

    秀潤社  1995 

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  • Genes for development, cell growth and infectious diseases

    John Libbey Eurotext  1995  （ ISBN:2742000631 ）

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MISC

  • 理工学系から見た医歯理工連携とその未来~なぜ東工大と東京医科歯科大学は大学統合したのか~

    廣田順二

    日本脳神経外傷学会プログラム・抄録集   48th   2025

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  • Molecular mechanisms for the generation of diversity of olfactory sensory neurons

    岩田哲郎, 廣田順二

    生体の科学   76 ( 4 )   2025

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  • Reconstruction of human T cell receptor gene locus using the Bacillus subtilis genome vector.

    諸角光祐, 岩田哲郎, 山崎憲政, 神沼修, 廣田順二

    日本農芸化学会大会講演要旨集(Web)   2024   2024

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  • テトロドトキシン類縁体によるトラフグ誘引活性の解明

    宮嵜海成, 横山雄彦, 佐藤繁, 高田健太郎, 周防玲, 糸井史朗, 廣田順二, 安立昌篤, 宮坂忠親, 西川俊夫

    日本水産学会大会講演要旨集(CD-ROM)   2024   2024

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  • 嗅覚受容体遺伝子発現におけるSsbp2の機能解明

    町田夏芽, 白川大地, 小出裕太郎, 小澤悠太, 小林千鶴, 福嶋俊明, 岩田哲郎, 廣田順二

    日本分子生物学会年会プログラム・要旨集(Web)   47th   2024

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  • Phenotypic analysis of ancV1R-deficient male mice.

    武田紗季, 近藤宏, 岩田哲朗, 二階堂雅人, 廣田順二

    日本農芸化学会大会講演要旨集(Web)   2024   2024

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  • Functional analysis of Ssbp2 in odorant receptor gene expression

    町田夏芽, 白川大地, 小林千鶴, 福嶋俊明, 岩田哲郎, 廣田順二

    日本分子生物学会年会プログラム・要旨集(Web)   45th   2022

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  • Characterization of early-born neurons in the mouse olfactory epithelium

    内田樹菜, 岩田哲郎, 廣田順二

    日本分子生物学会年会プログラム・要旨集(Web)   45th   2022

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  • Expression of a transcription factor Eya1 in bitter taste receptor cells

    應本真, 北本颯希, 廣田順二, 廣田順二

    日本農芸化学会大会講演要旨集(Web)   2021   2021

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  • Mechanism of odorant receptor class choice in mice Invited Reviewed

    榎本孝幸, 廣田順二

    Aroma Research   21 ( 1 )   76 - 81   2020.1

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  • Molecular Mechanisms Underlying Diversification of Olfactory Sensory Neurons Invited

    廣田順二

    季刊香料   284 ( 284 )   59 - 65   2019.12

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  • 嗅覚受容体の遺伝子クラスター Invited

    岩田哲郎, 廣田順二

    Clinical Neuroscience   37 ( 12 )   1432 - 1435   2019.12

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  • 嗅覚受容体の遺伝子発現制御機構

    廣田順二

    日本生化学会大会(Web)   92nd   2019

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  • 匂い受容体遺伝子の新たな発現制御領域の発見~匂い受容体の遺伝子進化の謎の解明へ~

    岩田哲郎, 廣田順二

    Aroma Research   19 ( 2 )   128‐129   2018.5

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  • 匂い受容体巨大遺伝子クラスターを制御するゲノム領域の発見

    岩田哲郎, 廣田順二

    バイオサイエンスとインダストリー   76 ( 3 )   232‐233   2018.5

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  • 舌だけではない！体を守る味細胞 - 生体防御に関わる化学感覚細胞のマスター因子を発見 Invited Reviewed

    廣田 順二

    academist Journal   2018

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  • 広範な脊椎動物に共通に存在するフェロモン受容体遺伝子の進化解析

    依田涼太, 鈴木彦有, 岩田哲郎, 廣田順二, 二階堂雅人

    日本進化学会大会プログラム・講演要旨集(Web)   20th   2018

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  • 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

    岩田哲郎, 新村芳人, 新村芳人, 小林千鶴, 白川大地, 鈴木彦有, 榎本孝幸, 東原和成, 東原和成, 吉原良浩, 吉原良浩, 廣田順二, 廣田順二

    日本遺伝学会大会プログラム・予稿集   90th   2018

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  • 広範な脊椎動物が共有する新規フェロモン受容体の進化と機能

    鈴木彦有, 鈴木彦有, 岩田哲郎, 依田涼太, 廣田順二, 二階堂雅人

    日本進化学会大会プログラム・講演要旨集(Web)   19th   77 (WEB ONLY)   2017.8

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  • Pou2f3/Skn-1a is required for the functional differentiation of Trpm5-expressing cells in multiple tissues Reviewed

    Junpei Yamashita, Makoto Ohmoto, Tatsuya Yamaguchi, Ichiro Matsumoto, Junji Hirota

    CHEMICAL SENSES   41 ( 9 )   E136 - E136   2016.11

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  • Expression analysis of Bcl11b in Xenopus tropicalis olfactory epithelium Reviewed

    Kanako Nakayama, Hikoyu Suzuki, Masato Nikaido, Takayuki Enomoto, Junji Hirota

    CHEMICAL SENSES   41 ( 9 )   E201 - E202   2016.11

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  • Studies on the cis-element for mouse class I odorant receptor genes using the Bacillus subtilis genome vector Reviewed

    Tetsuo Iwata, Shinya Kaneko, Takafumi Ogawa, Chizuru Kobayashi, Yuh Shiwa, Takayuki Enomoto, Hirofumi Yoshikawa, Junji Hirota

    CHEMICAL SENSES   41 ( 9 )   E208 - E208   2016.11

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  • Functional analysis of CTCF in odorant receptor gene expression in mice Reviewed

    Chizuru Kobayashi, Tetsuo Iwata, Niles Galjart, Junji Hirota

    CHEMICAL SENSES   41 ( 9 )   E248 - E248   2016.11

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  • 広範な脊椎動物に共有される新規V1R受容体遺伝子

    鈴木彦有, 鈴木彦有, 依田涼太, 中山叶子, 岩田哲郎, 村田健, 東原和成, 廣田順二, 二階堂雅人

    日本進化学会大会プログラム・講演要旨集(Web)   18th   ROMBUNNO.O‐1A‐2 (WEB ONLY)   2016.8

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  • 遺伝子からみた匂いの感覚

    廣田順二

    Aroma Research   16 ( 2 )   172 - 175   2015.5

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  • The fate control of olfactory sensory neurons

    16 ( 2 )   172 - 175   2015

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  • RecA誘導型枯草菌ゲノムベクターシステムの開発とトランスジェネシスへの応用

    小河貴郁, 岩田哲郎, 金子真也, 板谷光泰, 廣田順二

    日本分子生物学会年会プログラム・要旨集(Web)   37th   3LBA-30 (WEB ONLY)   2014

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  • 心に触れる匂いの記憶

    廣田 順二

    日本味と匂学会誌   20 ( 3 )   189 - 190   2013.12

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  • RecA誘導型枯草菌ゲノムベクターシステムの開発

    小河貴郁, 岩田哲郎, 金子真也, 廣田順二

    日本分子生物学会年会プログラム・要旨集(Web)   36th   1P-0954 (WEB ONLY)   2013

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  • 合成ゲノムベクターを用いたマウス遺伝子改変

    岩田哲郎, 金子真也, 廣田順二

    日本農芸化学会大会講演要旨集(Web)   2012   4SY19-4 (WEB ONLY)   2012.3

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  • Application of Bacillus subtilis genome vector for mouse genetic engineering Reviewed

    Shinya Kaneko, Tetsuro Iwata, Junji Hirota, Mitsuhiro Itaya

    GENES & GENETIC SYSTEMS   86 ( 6 )   396 - 396   2011.12

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  • ゲノムベクターを用いたマウス遺伝子改変操作への適用

    金子真也, 岩田哲郎, 廣田順二, 板谷光泰

    日本遺伝学会大会プログラム・予稿集   83rd   70   2011.8

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  • ヒト水棲型嗅覚受容体の機能解析と新たな水溶性匂い分子の探索

    廣田順二

    三島海雲記念財団研究報告書   ( 47 )   26 - 28   2010.11

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  • バイオイメージングに向けた長残光性蛍光ナノ粒子の作製と光学特性

    吉村文孝, 廣田順二, 中村一隆, 若井史博, 吉本護, 小田原修, 和田裕之

    セラミックス基礎科学討論会講演要旨集   48th   2010

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  • Expression of Bcl11b in the mouse olfactory system

    ENOMOTO Takayuki, KOMINAMI Ryo, HIROTA Junji

    The Japanese journal of taste and smell research   15 ( 3 )   569 - 572   2008.12

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  • ISOT2008 in San Francisco に参加して

    廣田 順二

    日本味と匂学会誌 = The Japanese journal of taste and smell research   15 ( 3 )   691 - 692   2008.12

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  • Expression of Bcl11b in the developing mouse olfactory system Reviewed

    Takayuki Enomoto, Ryo Kominami, Junji Hirota

    NEUROSCIENCE RESEARCH   61   S106 - S106   2008

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  • Differential impact of Lhx2 deficiency on expression of class I and class II odorant receptor genes

    HIROTA Junji, OMURA Masayo, MOMBAERTS Peter

    The Japanese journal of taste and smell research   14 ( 3 )   549 - 552   2007.12

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  • Function of Bcl11b in the mouse vomeronasal system

    ENOMOTO Takayuki, KOMINAMI Ryo, HIROTA Junji

    The Japanese journal of taste and smell research   14 ( 3 )   553 - 556   2007.12

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  • Evolution and regulation of odorant receptor genes

    Hirota Junji

    Jpn J Taste Smell Res   14 ( 2 )   179 - 186   2007

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    嗅覚は、生命維持のために必要な動物の行動に密接に関与し、進化の過程で原始から現代に至るまで保存されてきた感覚である。匂い分子を感知する嗅覚受容体は、水棲から陸棲への生活環境の変化に伴って分子進化を遂げ、また社会環境の複雑化に対応するためにその遺伝子数を増加させてきたのではないかと考えられる。マウス嗅上皮には、魚類に由来するClass I嗅覚受容体遺伝子と、そこから派生したと考えられる陸棲動物特異的Class II 嗅覚受容体遺伝子の両方が発現している。本稿では、2つに分類される嗅覚受容体遺伝子とそれらの遺伝子発現制御機構について、最近の知見を交えて解説したい。

    DOI： 10.18965/tasteandsmell.14.2_179

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  • STSマウス4番染色体上の新規放射線リンパ腫抵抗性領域

    森展子, 三瀧優子, 木下育子, 廣田順二, 山手丈至, 奥本正昭

    日本放射線影響学会大会講演要旨集   48th   2005

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  • Role of inositol 1,4,5-trisphosphate (IP3) receptor/Ca2+ signaling in cell function Reviewed

    K Mikoshiba, T Furuichi, A Miyawaki, T Michikawa, M Yamamoto-Hino, J Hirota, K Takei, T Inoue, S Kume, M Matsumoto, A Muto

    CHALLENGES FOR NEUROSCIENCE IN THE 21ST CENTURY   22 ( 22 )   121 - 146   2000

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  • イオンチャネル研究の最前線 イノシトール3リン酸受容体チャネルの構造と生理機能

    道川 貴章, 廣田 順二, 山田 麻紀, 日野 美紀, 光山 冬樹, 岩崎 広英, 宮内 浩, 岩附 正人, 内山 剛, 内田 敬子, 横山 玲, 御子柴 克彦

    生化学   71 ( 8 )   594 - 594   1999.8

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  • イオン性シグナル伝達の解明に挑む イオンチャネル構造機能研究の新展開 IP3受容体-IP3誘導Ca2+放出チャネルの構造機能と発現

    古市 貞一, 道川 貴章, 吉川 文生, 平嶋 千恵, 水野 秀昭, 内山 剛, 岩附 正人, 井上 貴史, 廣田 順二, 日野 美紀

    神経化学   37 ( 3 )   261 - 261   1998.9

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  • アポトーシスの分子機構 アポトーシスに伴うイノシトール3リン酸受容体の限定分解

    廣田 順二, 古市 貞一, 御子柴 克彦

    生化学   70 ( 8 )   787 - 787   1998.8

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  • InsP(3) receptor and Ca2+ signaling Reviewed

    K Mikoshiba, T Furuichi, A Miyawaki, S Kume, A Muto, T Inoue, K Kohda, T Michikawa, J Hirota, T Monkawa, F Yoshikawa

    JOURNAL OF NEUROCHEMISTRY   69 ( 29 )   S256 - S256   1997

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  • IP3 Receptor Ca2+ Channel: Key Molecule of Ca2+ Signaling.

    御子柴克彦, 道川貴章, 吉川文生, 山田麻紀, 松本峰男, 広田順二, 武藤彩, 粂昭苑, 古市貞一

    生体膜と薬物の相互作用シンポジウム講演要旨集   19th   1997

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  • イノシトール三リン酸受容体のカルモジュリン結合解離反応の解析

    廣田 順二, 坂口 敬人, 曽田 裕行, 道川 貴章, 長谷川 幸雄, 古市 貞一, 御子柴 克彦

    日本分子生物学会年会プログラム・講演要旨集   19   519 - 519   1996.8

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  • イノシトール三リン酸受容体のCa^<2+>による活性制御機構の解析

    道川 貴章, 廣田 順二, 川野 誠子, 平岡 昌和, 古市 貞一, 御子柴 克彦

    日本分子生物学会年会プログラム・講演要旨集   19   519 - 519   1996.8

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    Language：Japanese  

    CiNii Books

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  • イノシートル三リン酸感受性Ca^<2+>放出チャンネルの構造・機能・発現

    古市 貞一, 道川 貴章, 廣田 順二, 山田 麻紀, 松本 峰男, 吉川 文生, 米島 宏幸, 安富 大祐, 井上 貴文, 御子柴 克彦

    日本分子生物学会年会プログラム・講演要旨集   19   29 - 29   1996.8

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    Language：Japanese  

    CiNii Books

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  • Inositol 1,4,5-trisphosphate receptor and Ca2+ signaling

    Atsushi Miyawaki, Teiichi Furuichi, Takayuki Michikawa, Shingo Yoshikawa, Shoen Kume, Akira Muto, Hideyuki Okano, Maki Yamada, Junji Hirota, Norihiko Yamada, Hiroyuki Yoneshima, Toshiaki Monkawa, Fumio Yoshikawa, Daisuke Furutama, Katushiko Mikoshiba

    Igaku-Shoin Medical Pub   154 - 164   1996

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  • Analysis of IP3 Receptor/Ca2+-Release Channel.

    広田順二, 幸田和久, 宮脇敦史, 古市貞一, 御子柴克彦

    細胞工学   13 ( 7 )   637 - 648   1994

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    Language：Japanese  

    J-GLOBAL

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Industrial property rights

  • 蛍光粒子およびその製造方法

    小野寺 裕司, 布川 貴史, 中村 一隆, 廣田 順二, 小田原 修, 和田 裕之

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    Applicant：国立大学法人東京工業大学

    Application no：特願2011-147041  Date applied：2011.7

    Announcement no：特開2013-014651  Date announced：2013.1

    J-GLOBAL

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  • 蛍光粒子およびその製造方法

    和田 裕之, 吉村 文孝, 小田原 修, 廣田 順二

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    Applicant：国立大学法人東京工業大学

    Application no：特願2010-001556  Date applied：2010.1

    Announcement no：特開2010-242059  Date announced：2010.10

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  • 細胞内Caイオンの機能制御

    御子柴 克彦, 廣田 順二, 安東 英明

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    Applicant：独立行政法人科学技術振興機構

    Application no：JP2003014004  Date applied：2003.10

    Announcement no：WO2004-103393  Date announced：2004.12

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  • 細胞内Caイオンの機能制御

    御子柴 克彦, 廣田 順二, 安東 英明

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    Applicant：独立行政法人科学技術振興機構

    Application no：特願2004-572136  Date applied：2003.10

    Patent/Registration no：特許第4472534号  Date issued：2010.3

    J-GLOBAL

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Awards

  • Best Teacher Award

    2019.2   Tokyo Institute of Technology  

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  • Seiichi Tejima Research Award

    2019.2  

    HIROTA Junji

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  • 竹田国際貢献賞

    2016.10   合成ゲノムベクターを用いたゲノム工学技術開発への国際的貢献

    廣田 順二

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  • 日本味と匂学会奨励賞

    2011.10   嗅覚受容体遺伝子発現と嗅覚系神経分化の分子機構に関する研究

    廣田 順二

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  • 日本味と匂学会論文賞

    2009.9  

    廣田 順二

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  • Human Frontier Science Program Long-Term Fellow

    2000.4  

    HIROTA Junji

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Research Projects

  • Molecular basis and its adaptive significance of ancV1R mediated pheromone detection in vertebrates

    Grant number：24K02074  2024.4 - 2027.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\17420000 （ Direct Cost: \13400000 、 Indirect Cost：\4020000 ）

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  • Establishment of mega-base synthetic genome manipulation using next generation genome engineering tools.

    Grant number：23K17990  2023.6 - 2026.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Research (Exploratory)

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    Grant amount：\6500000 （ Direct Cost: \5000000 、 Indirect Cost：\1500000 ）

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  • 核移植クローン技術に基づく免疫応答・疾患発症機構の包括的研究基盤

    Grant number：22H00398  2022.4 - 2026.3

    日本学術振興会  科学研究費助成事業  基盤研究(A)

    神沼 修, 田中 芳彦, 八村 敏志, 池田 健一郎, 廣田 順二, 坂口 剛正, 堀 正敏, 杉浦 一充, 井上 貴美子, 細見 直永, 三浦 健人, 一戸 辰夫

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    Grant amount：\41990000 （ Direct Cost: \32300000 、 Indirect Cost：\9690000 ）

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  • The origin and mechanism of pheromone reception elucidated by novel vomeronasal receptor ancV1R

    Grant number：20H03307  2020.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\16380000 （ Direct Cost: \12600000 、 Indirect Cost：\3780000 ）

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  • 母子間化学コミュニケーションを促進する羊水成分の同定と生理機能の解明

    Grant number：20H04768  2020.4 - 2022.3

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    廣田 順二

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    動物の化学コミュニケーションの一つに匂い物質を介した母子間コミュニケーションがある。例えば、哺乳動物の新生仔は、「母の匂い」を手掛かりに初期哺乳行動をとる。その「母の匂い」の源の一つとされているのが羊水である。これまでの研究で、羊水には胎生動物の新生仔が嗜好性を示す匂い物質が存在し、またヒト新生児を含め産まれたばかりの子に安寧効果をもたらすことが報告されている。本研究では、羊水中に含まれる母子間化学コミュニケーションを媒介する匂い分子の同定と生理機能の解明を目的とした。これまでにマウス、犬、牛の羊水をGC/MS解析をおこない、羊水の匂い成分中に共通する複数の脂肪酸を見出した。マウスの不安様行動解析の結果、このうちの一つの脂肪酸にマウスの不安様行動を緩和する効果が認められた。この脂肪酸によって活性化される脳（嗅球）の発火パターンを解析した結果、発火部位は極めて限られており、少数の嗅覚受容体がこの物質を受容していることがわかった。さらに羊水成分を受容する嗅覚受容体を同定するために、嗅覚受容体のmRNAレベルが長時間のリガンド暴露によって減少する現象を利用した受容体同定法、DREAM法（Deorphanization of receptors based on expression alterations in mRNA levels technique）を用いた解析をおこなった結果、複数の候補受容体分子を得たが、期間内に再構築系を用いたリガンド応答確認による受容体の同定には至らなかった。今後、再構築系を用いたリガンド応答、ならびに神経活動マーカーと受容体の共発現の有無を確認することで、受容体を同定し、さらにゲノム編集技術を用いたノックアウトマウスの作成に着手し、生理機能の解明をおこなう予定である。

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  • Genetic manipulation of odorant receptor class choice and olfactory behaivor

    Grant number：19H03264  2019.4 - 2023.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

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    Grant amount：\17290000 （ Direct Cost: \13300000 、 Indirect Cost：\3990000 ）

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  • 嗅覚受容体とβグロビン、２つの遺伝子クラスターが織りなすクロマチンポテンシャル

    Grant number：19H05256  2019.4 - 2021.3

    日本学術振興会  科学研究費助成事業  新学術領域研究(研究領域提案型)

    廣田 順二

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    Grant amount：\5200000 （ Direct Cost: \4000000 、 Indirect Cost：\1200000 ）

    マウスのクラス１嗅覚受容体遺伝子は129個あり、第７染色体上に巨大な遺伝子クラスターを形成する。クラス１嗅覚受容体遺伝子の転写調節配列として我々が同定したJ elementは、この巨大遺伝子クラスター全体を制御しており、制御する”遺伝子数”と”ゲノム上の距離”の両方において他に類を見ない規模で遺伝子発現を制御する。しかし、J elementの超長距離作用性の分子機構は明らかになっていない。本研究では、まずJ element（1.3 kb）の機能解析をさらにすすめ、J element配列内の330 bp（Core J element）がクラス１特異的なエンハンサー活性に必要十分であること明らかにした。Core J elementのモチーフ配列解析の結果、 O/E-like配列とホメオドメイン配列からなるCompositeモチーフがエンハンサー活性に必須であった。
    クラス１嗅覚受容体クラスターは、βグロビンクラスターを内包する。J elementの超長距離作用性を可能にする分子基盤を明らかにするため、進化的に保存された２つの遺伝子クラスターの機能的相互作用の解析をおこなうこととし、クラス１嗅覚受容体クラスター欠失変異マウスと嗅神経細胞特異的βグロビンクラスター欠失マウスの作出をおこなった。これまでにβグロビンクラスターのテロメア側にあるクラス１嗅覚受容体クラスター（1.3Mb）欠失マウス、嗅神経細胞特異的βグロビンクラスター欠失マウスの作出に成功した。一方、セントロメア側のクラス１嗅覚受容体クラスター（1.5Mb）の欠失変異は胎生致死であったため、クラスター内に存在する嗅覚受容体遺伝子以外の遺伝子を残しつつ、クラス１嗅覚受容体クラスターを欠失させることにした。今後、これらのクラスター欠失マウスにおける遺伝子発現解析を行い、２つの遺伝子クラスター間の機能的相互作用を明らかにする。

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  • Molecular mechanisms of mouse mother-pup communication

    Grant number：18H04610  2018.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

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    Grant amount：\4680000 （ Direct Cost: \3600000 、 Indirect Cost：\1080000 ）

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  • Molecular mechanism of odorant receptor class choice in mice

    Grant number：16K07366  2016.4 - 2020.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    Hirota Junji

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    Grant amount：\4940000 （ Direct Cost: \3800000 、 Indirect Cost：\1140000 ）

    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.

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  • Functional analysis on novel pheromone receptor gene ancV1R, which is shared among most vertebrates

    Grant number：16H04820  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (B)

    Nikaido Masato

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    Grant amount：\15730000 （ Direct Cost: \12100000 、 Indirect Cost：\3630000 ）

    We found a novel pheromone receptor gene belonging to the V1R family, named ancV1R, which is shared among most Osteichthyes (bony vertebrates) from the basal lineage of ray-finned fishes to mammals. Phylogenetic and syntenic analyses of ancV1R using 115 vertebrate genomes revealed that it represents an orthologous gene conserved for >400 million years of vertebrate evolution. Interestingly, the loss of ancV1R in some tetrapods is coincident with the degeneration of the vomeronasal organ (VNO) in higher primates, cetaceans, and some reptiles including birds and crocodilians. In addition, ancV1R is expressed in most mature vomeronasal sensory neurons (VSNs) in contrast with canonical V1Rs, which are sparsely expressed in a manner that is consistent with the “one neuron one receptor” rule. Our results imply that a previously undescribed V1R gene inherited from an ancient Silurian ancestor may have played an important functional role in the evolution of vertebrate VNO.

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  • Regulation of innate olfactory behavior by genetic manipulation of Bcl11b gene

    Grant number：16K18361  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    Enomoto Takayuki, Hirota Junji

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    Olfaction is important for the survival of animals. Olfactory sensory neurons (OSNs) are subdivided into two types, which detect odorous chemicals from the external environment. The zinc finger transcription factor Bcl11b regulates a cell fate determination of two OSN-types in the development. In this study, we examined physiological and behavioral responses to odorants on OSN-specific loss-of- and gain-of-Bcl11b function mutant mice. From analyses of these mutant mice, we demonstrate that the changes of peripheral neural input influences on an innate olfactory aversion behavior in mice.

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  • Development of Bacillus subtilis genome vector-based complete manipulation and reconstruction of genomic DNA

    Grant number：25660289  2013.4 - 2016.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Challenging Exploratory Research

    Hirota Junji, KANEKO Shinya

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    Grant amount：\4030000 （ Direct Cost: \3100000 、 Indirect Cost：\930000 ）

    In this study, we established a complete genetic modification method for the BGM vector system, including insertion, deletion, inversion and fusion, to engineer genomic DNA fragments without any trace of modifications. In addition, we demonstrated that this system can be used for mouse transgenesis. Thus, the BGM vector system can be an alternative platform for engineering large DNA fragments in addition to conventional systems such as bacterial and yeast artificial
    chromosomes. Using this system, we provided the first experimental evidence of a cis-acting element for a class I OR gene.In addition, to manipulate large DNA fragments more stably than the conventional BGM vector, we developed a novel BGM vector with inducible recA expression system, iREX. We demonstrated that the iREX can be applied to handling the DNA, which has severalhomologous sequences, such as multiple-reporter expression cassettes.

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  • Functional analysis of class I odorant receptors and their ligands

    Grant number：21200010  2009 - 2011

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)

    HIROTA Junji

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    Grant amount：\30940000 （ Direct Cost: \23800000 、 Indirect Cost：\7140000 ）

    The vertebrate olfactory system recognizes millions of environmental chemicals and perceives them as odors. Olfactory sensory neurons, the primary sensory neurons in the olfactory system, initiate the perception process by detecting odorants, which interact with odorant receptors (ORs). ORs belong to the largest gene superfamily present in any genome analyzed so far. OR genes are classified into two classes. Class I ORs, which are fish-like and phylogenetically more ancient receptors bind aqueous odorant molecules. The other type is called class II ORs, which are specific to terrestrial animals seem to bind volatile odorant molecules. Although class I ORs in terrestrial mammals had been considered as a relic of evolution from fish to terrestrial, recent studies have demonstrated that intact and functional genes still remain, suggesting that class I Ors in terrestrial mammals might have important physiological functions. In this study, we investigated function of class I Ors in terrestrial mammals to identify aqueous odorous molecules. We focused on amniotic fluid (AF) as source for aqueous odorants. AF is maternal fluid in uterus protecting embryo that is the only aquatic environment for terrestrial mammals. We demonstrated that AF contains some aqueous odor molecules through mouse behavior analyses, histochemical and physiological studies. In addition, we established transgenic lines which enable to visualize class I OR transgene expression and OSN axonal projections, providing the first experimental evidence of a cis-acting element for a class I OR gene. This transgenic mice can be useful tool not only for screening ligands of class I OR but also for study on class I OR gene regulation.

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  • Regulation of odorant receptor gene expression

    Grant number：20570208  2008 - 2010

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HIROTA Junji

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    Grant amount：\4290000 （ Direct Cost: \3300000 、 Indirect Cost：\990000 ）

    To study molecular mechanisms underlying odorant receptor (OR) gene expression in mice, we have screened transcription factors which might be involved in OR gene regulation, and have made transgenic mice to identify promoter/enhancer regions. We found a few candidate factors which may regulate OR gene expression. In addition, we have constructed transgenes to identify regulatory regions OR genes, and have obtained several transgenic lines.

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  • Function of LIM homeodomain protein Lhx2 in odorant receptor gene regulation

    Grant number：18570206  2006 - 2007

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

    HIROTA Junji, ANTHONY Perry

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    Grant amount：\3900000 （ Direct Cost: \3600000 、 Indirect Cost：\300000 ）

    Odorant receptor (OR) genes can be classified into two types: fish-like class I OR genes and terrestrial-specific class II OR genes. We have previously shown that Lhx2, a LIM-homeodomain protein, binds to the homeodomain site in the promoter region of mouse M71, a class II OR, and that a knockout mutation in Lhx2 precludes expression of all tested class II OR genes including M71. Here, we report that most class I OR genes, which are expressed in a dorsal region of the olfactory epithelium, are still expressed in Lhx2-deficient embryos. There are two exceptions: two class I OR genes, which are normally expressed in a more ventral region, are no longer expressed in Lhx2 mutant mice. Lhx2 is transcribed in olfactory sensory neurons irrespective of expression of class I or class II OR genes. Thus, a deficiency of Lhx2has a differential impact on class I and class II OR gene expression, suggesting that two distinct pathways underlie OR gene expression in mouse.

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