Elucidation of genetic program controlling cerebellar neural circuit formation

• Project/Area Number: 18H02448
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Nagoya University
• Principal Investigator: Hibi Masahiko 名古屋大学, 理学研究科, 教授 (40273627)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000); Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 発生・分化 / 神経科学 / 脳・神経 / 遺伝学 / 遺伝子

Outline of Final Research Achievements

Neurons in functional neural circuits are generated from neural stem cells or neural progenitor cells during development. However, the mechanisms of differentiation from these cells into individual types of neurons that form complex neural circuit structures is still largely unknown. In this study, we focused on cerebellar Purkinje cells and their input cells, the neurons in the inferior olivary nucleus, which constitute cerebellar neural circuits, and elucidated part of the genetic program that controls the differentiation of these neurons and the formation of neural circuits.

Academic Significance and Societal Importance of the Research Achievements

動物の複雑な行動を制御する神経回路は遺伝プログラムに従って形成される。本研究では、小脳神経回路をモデルとして、小脳神経回路を構成するプルキンエ細胞と下オリーブ核ニューロンの、細胞分化や神経回路形成を制御する遺伝プログラムの一端を解明した。本研究は、多様な神経細胞が産生される発生生物学のメカニズムを明らかにするだけでなく、小脳神経回路の異常によって引き起こされる種々のヒト疾患の病態解明や治療法の開発にも貢献する可能性がある。

Research Products

• [Int'l Joint Research] University of South Carolina(米国)
• [Journal Article] Morphological analysis of the cerebellum and its efferent system in a basal actinopterygian fish, Polypterus senegalus (2022)
  • Author(s): Ikenaga Takanori、Shimomai Rinko、Hagio Hanako、Kimura Satoru、Matsumoto Kazumasa、Kato Dai‐ichiro、Uesugi Kentaro、Takeuchi Akihisa、Yamamoto Naoyuki、Hibi Masahiko
  • Journal Title: Journal of Comparative Neurology Volume: 530 Issue: 8 Pages: 1231-1246
  • DOI: 10.1002/cne.25271
  • Peer Reviewed
• [Journal Article] Involvement of Cerebellar Neural Circuits in Active Avoidance Conditioning in Zebrafish (2021)
  • Author(s): Wataru Koyama, Ryo Hosomi, Koji Matsuda, Koichi Kawakami, Masahiko Hibi, Takashi Shimizu
  • Journal Title: eNeuro Volume: 8 Issue: 3 Pages: 0507-0520
  • DOI: 10.1523/eneuro.0507-20.2021
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cfdp1 controls the cell cycle and neural differentiation in the zebrafish cerebellum and retina (2021)
  • Author(s): Tsubasa Itoh, Shinsuke Inoue, Xiaoding Sun, Ryo Kusuda, Masahiko Hibi, Takashi Shimizu
  • Journal Title: Developmental Dynamics Volume: 250 Issue: 11 Pages: 1618-1633
  • DOI: 10.1002/dvdy.371
  • Peer Reviewed
• [Journal Article] Maintenance of quiescent oocytes by noradrenergic signals (2021)
  • Author(s): Jeongho Kim, Moonjung Hyun, Masahiko Hibi, Young-Jai You
  • Journal Title: Nature Communications Volume: 12 Issue: 1 Pages: 6925-6925
  • DOI: 10.1038/s41467-021-26945-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular properties of new enzyme rhodopsins with PDE activity (2020)
  • Author(s): Sugiura M., Tsunoda SP., Hibi M., Kandori H
  • Journal Title: ACS Omega Volume: 5 Issue: 18 Pages: 10602-10609
  • DOI: 10.1021/acsomega.0c01113
  • Peer Reviewed / Open Access
• [Journal Article] Functionally distinct Purkinje cell types show temporal precision in encoding locomotion (2020)
  • Author(s): Weipang Chang, Andrea Pedroni, Victoria Hohendorf, Stefania Giacomello, Masahiko Hibi, Reinhard W. Koster, Konstantinos Ampatzis
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 117 Issue: 29 Pages: 17330-17337
  • DOI: 10.1073/pnas.2005633117
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Gsx2 is required for specification of neurons in the inferior olivary nuclei from Ptf1a-expressing neural progenitors in zebrafish. (2020)
  • Author(s): Itoh T, Takeuchi M, Sakgami M, Asakawa K, Sumiyama K, Kawakami K, Shimizu T, Hibi M.
  • Journal Title: Development Volume: 147
  • DOI: 10.1242/dev.190603
  • Peer Reviewed / Open Access
• [Journal Article] Syntaphilin-Mediated Docking of Mitochondria at the Growth Cone Is Dispensable for Axon Elongation In Vivo (2019)
  • Author(s): Tine Verreet , Cory J Weaver , Hiromu Hino , Masahiko Hibi, Fabienne E Poulain
  • Journal Title: eNeuro Volume: 6 Issue: 5 Pages: ENEURO.0026-19.2019
  • DOI: 10.1523/eneuro.0026-19.2019
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Reelin in cell positioning in the cerebellum and the cerebellum-like structure in zebrafish. (2019)
  • Author(s): Nimura T, Itoh T, Hagio H, Hayashi T, Di Donato V, Takeuchi M, Itoh T, Inoguchi F, Sato Y, Yamamoto N, Katsuyama Y, Del Bene F, Shimizu T, Hibi M.
  • Journal Title: Dev Biol. Volume: 455 Issue: 2 Pages: 393-408
  • DOI: 10.1016/j.ydbio.2019.07.010
  • NAID: 120006808762
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tracing of Afferent Connections in the Zebrafish Cerebellum Using Recombinant Rabies Virus (2019)
  • Author(s): Dohaku Ryuji、Yamaguchi Masahiro、Yamamoto Naoyuki、Shimizu Takashi、Osakada Fumitaka、Hibi Masahiko
  • Journal Title: Frontiers in Neural Circuits Volume: 13 Pages: 1-15
  • DOI: 10.3389/fncir.2019.00030
  • Peer Reviewed / Open Access
• [Journal Article] Color opponency with a single kind of bistable opsin in the zebrafish pineal organ (2018)
  • Author(s): Wada Seiji、Shen Baoguo、Kawano-Yamashita Emi、Nagata Takashi、Hibi Masahiko、Tamotsu Satoshi、Koyanagi Mitsumasa、Terakita Akihisa
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 115 Issue: 44 Pages: 11310-11315
  • DOI: 10.1073/pnas.1802592115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Madagascar ground gecko genome analysis characterizes asymmetric fates of duplicated genes (2018)
  • Author(s): Hara Y, Takeuchi M, Kageyama Y, Tatsumi K, Hibi M, Kiyonari H, Kuraku S.
  • Journal Title: BMC Biology Volume: 16 Issue: 1 Pages: 40-40
  • DOI: 10.1186/s12915-018-0509-4
  • Peer Reviewed / Open Access
• [Journal Article] Distinct interactions of Sox5 and Sox10 in fate specification of pigment cells in medaka and zebrafish. (2018)
  • Author(s): Nagao Y, Takada H, Miyadai M, Adachi T, Seki R, Kamei Y, Hara I, Taniguchi Y, Naruse K, Hibi M, Kelsh RN, Hashimoto H
  • Journal Title: PLoS Genetics Volume: 14(4) Issue: 4 Pages: 1007260-1007260
  • DOI: 10.1371/journal.pgen.1007260
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Role of transcription factors Skor1b/2 and Foxp1b/4 in differentiation of Purkinje cells in zebrafish (2021)
  • Author(s): Itoh, T., Yura, S., Nakanishi, A., Uehara, M., Shimizu, T., Hibi, M.
  • Organizer: 第54回 日本発生生物学学会年会
• [Presentation] Molecular mechanisms of Purkinje cell differentiation mediated by transcriptional regulators (2021)
  • Author(s): Uehara, M., Itoh., T., Yura, S., Nakanishi, A., Shimizu, T., Hibi, M.
  • Organizer: The 27th Japanese Medaka and Zebrafish Meeting
• [Presentation] Molecular mechanisms that control differentiation of Purkinje cells in zebrafish (2020)
  • Author(s): Itoh, T., Yura, S., Nakanishi, A., Uehara, M., Shimizu, T., Hibi, M.
  • Organizer: The 26th Japanese Medaka and Zebrafish Meeting
• [Presentation] 小型魚類を用いた小脳神経回路の形成と機能の解析 (2019)
  • Author(s): 日比正彦
  • Organizer: 第一回小脳システム研究会シンポジウム
  • Invited
• [Presentation] Generation of novel optogenetic tools controlling intracellular second messengers in neurons (2019)
  • Author(s): Hagio H, Matsuda K, Shimizu T, Nagata T, Koyanagi M, Terakita A, Hibi M
  • Organizer: 第25回小型魚類研究会
• [Presentation] Differentiation of inferior olivary nucleus neurons and Purkinje cells from Ptf1a-expressing progenitors (2019)
  • Author(s): Itoh T, Yura S, Takeuchi M, Sakagami M, Shimizu T, Hibi M
  • Organizer: 第25回小型魚類研究会
• [Presentation] Development and function of zebrafish cerebellar neural circuitry (2019)
  • Author(s): Hibi M, Itoh T, Yura S, Matsuda K, Shimizu T
  • Organizer: NEURO2019（第42回日本神経科学大会、第62回日本神経化学会大会）
• [Presentation] Development and function of zebrafish cerebellar neural circuits (2019)
  • Author(s): Hibi M, Itoh T, Yura S, Matsuda K, Shimizu T
  • Organizer: Gordon Research Conference
  • Int'l Joint Research
• [Presentation] Roles of transcriptional regulators Foxp1b/Foxp4 and Skor1b/Skor2 in differentiation of Purkinje cells in the zebrafish cerebellum (2019)
  • Author(s): Yura S, Itoh T, Shimizu T, Hibi M
  • Organizer: 第52回日本発生生物学大会
• [Presentation] Cfdp1 regulates cell cycle and differentiation of granule cells in the zebrafish cerebellum (2019)
  • Author(s): Shimizu T, Inoue S, Sun X, Hibi M
  • Organizer: 第52回日本発生生物学大会
• [Presentation] Molecular mechanisms for differentiation of the inferior olivary nucleus neurons in zebrafish (2019)
  • Author(s): Itoh T, Takeuchi M, Sakagami M, Shimizu T, Hibi M
  • Organizer: 第52回日本発生生物学大会
• [Presentation] Transcriptional regulators controlling formation of the cerebellar neural circuits. (2018)
  • Author(s): Hibi M, Itoh T, Yura S, Matsuda K, Shimizu T
  • Organizer: 5th Imaging Structure and Function in the Zebrafish Brain Conference
  • Int'l Joint Research
• [Presentation] Genetic control for development of the inferior olive nucleus neurons in zebrafish. (2018)
  • Author(s): Itoh T, Takeuchi M, Sakagami M, Asakawa K, Kawakami K, Shimizu T, Hibi M
  • Organizer: 13th International Zebrafish Conference
  • Int'l Joint Research
• [Presentation] Involvement of axonal transport of Reelin in the layer and the neural circuit formation of the cerebellum and the optic tectum. (2018)
  • Author(s): Hibi M, Nimura T, Itoh T, Hayashi T, Takeuchi M, Di Donata V, Del Bene F, Shimizu T.
  • Organizer: 13th International Zebrafish Conference
  • Int'l Joint Research
• [Presentation] The cerebellar neural circuits differentially regulate freezing and active avoidance responses in the classical fear conditioning. (2018)
  • Author(s): Matsuda K, Yoshida M, Hosomi R, Tanabe H, Kawakami K, Hibi M, Shimizu T
  • Organizer: 13th International Zebrafish Conference
  • Int'l Joint Research
• [Presentation] Optogenetic manipulation of zebrafish neural circuits toward understanding higher order function of the cerebellum. (2018)
  • Author(s): Shimizu T, Matsuda K, Hibi M
  • Organizer: 第56回日本生物物理学会年会
  • Int'l Joint Research
• [Presentation] Role of axonal transport of Reelin in layer and neural circuit formation in the cerebellum and the optic tectum. (2018)
  • Author(s): Nimura T, Di Donata V, Hayashi T, Takeuchi M, Shimizu T, Del Bene F, Hibi M
  • Organizer: 第70回日本細胞生物学会第51回日本発生生物学会合同学会
• [Presentation] Fat2 controls formation of cerebellar neural circuits in zebrafish. (2018)
  • Author(s): Dohaku R, Takeuchi M, Shimizu T, Hibi M
  • Organizer: 第70回日本細胞生物学会第51回日本発生生物学会合同学会
• [Presentation] Molecular mechanisms that control development of the inferior olive nucleus neurons in zebrafish. (2018)
  • Author(s): Itoh T, Takeuchi M, Sakagami M, Asakawa K, Kawakami K, Shimizu T, Hibi M
  • Organizer: 第70回日本細胞生物学会第51回日本発生生物学会合同学会