General mechanisms controlling development of cerebellar neural circuits in vertebrates

• Project/Area Number: 15H04376
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Developmental biology
• Research Institution: Nagoya University
• Principal Investigator: HIBI MASAHIKO 名古屋大学, 生物機能開発利用研究センター, 教授 (40273627)
• Co-Investigator(Renkei-kenkyūsha): TAKEUCHI MIKI 名古屋大学, 生物機能開発利用研究センター, 研究員 (60625127)
• Research Collaborator: SHIMIZU TAKASHI 名古屋大学, 生物機能開発利用研究センター, 准教授 (50324760)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
• Keywords: 小脳 / 神経回路形成 / ゼブラフィッシュ / 神経発生 / 神経分化 / 層形成 / 転写因子 / 可視化 / 発生・分化 / 神経科学 / 脳・神経 / 遺伝学 / 遺伝子 / 蛍光タンパク質 / 変異体 / イメージング

Outline of Final Research Achievements

Using zebrafish as a main model system, (1) we isolated granule cell- and Purkinje cell-specific genes by RNA-seq. We found that (2) Contactin1b is involved in neural circuit formation for motor learning and motor coordination; (3) Reeling signaling is involved in migration of Purkinje cells in the cerebellum and type I neurons in the optic tectum, Reelin is transported through granule cell axons; (4) the transcription factors Ptf1a and Gsx2 are required for differentiation of neurons in the inferior olive nuclei, the expression of gsx2 is regulated by retinoic acid signaling; (5) the transcription factors Fop1b/4 and the transcriptional co-repressors Skor1b/2 function as master regulators in differentiation of Purkinje cells.

Research Products

• [Int'l Joint Research] Fred Hutchinson Cancer Research Center(米国)
• [Int'l Joint Research] コロンビア大学(米国)
• [Int'l Joint Research] 国立がん研究所(韓国)
• [Int'l Joint Research]
• [Journal Article] Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum (2018)
  • Author(s): Kidwell Chelsea U.、Su Chen-Ying、Hibi Masahiko、Moens Cecilia B.
  • Journal Title: Developmental Biology Volume: 印刷中 Issue: 1 Pages: 44-56
  • DOI: 10.1016/j.ydbio.2018.03.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Roles of maternal wnt8a transcripts in axis formation in zebrafish (2018)
  • Author(s): Hino Hiromu、Nakanishi Akiko、Seki Ryoko、Aoki Tsubasa、Yamaha Etsuro、Kawahara Atsuo、Shimizu Takashi、Hibi Masahiko
  • Journal Title: Developmental Biology Volume: 434 Issue: 1 Pages: 96-107
  • DOI: 10.1016/j.ydbio.2017.11.016
  • NAID: 120006808763
  • Peer Reviewed
• [Journal Article] Granule cells control recovery from classical conditioned fear responses in the zebrafish cerebellum (2017)
  • Author(s): Matsuda, K., Yoshida, M., Kawakami, K., Hibi, M., and Shimizu. T.
  • Journal Title: Scientific reports Volume: 7 Issue: 1 Pages: 11865-11865
  • DOI: 10.1038/s41598-017-10794-0
  • Peer Reviewed / Open Access
• [Journal Article] Medaka and zebrafish contactin1 mutants as a model for understanding neural circuits for motor coordination (2017)
  • Author(s): Takeuchi Miki、Inoue Chikako、Goshima Akiko、Nagao Yusuke、Shimizu Koichi、Miyamoto Hiroki、Shimizu Takashi、Hashimoto Hisashi、Yonemura Shigenobu、Kawahara Atsuo、Hirata Yutaka、Yoshida Masayuki、Hibi Masahiko
  • Journal Title: Genes to Cells Volume: 22 Issue: 8 Pages: 723-741
  • DOI: 10.1111/gtc.12509
  • NAID: 120006367981
  • Peer Reviewed / Open Access
• [Journal Article] Evolutionary mechanisms that generate morphology and neural-circuit diversity of the cerebellum. (2017)
  • Author(s): Hibi M, Matsuda K, Takeuchi M, Shimizu T, Murakami Y.
  • Journal Title: Development, Growth & Differentiation Volume: 印刷中 Issue: 4 Pages: 228-243
  • DOI: 10.1111/dgd.12349
  • NAID: 120006406681
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Oncogenic role of rab escort protein 1 through EGFR and STAT3 pathway. (2017)
  • Author(s): Yun UJ, Sung JY, Park SY, Ye SK, Shim J, Lee JS, Hibi M, Bae YK, Kim YN.
  • Journal Title: Cell Death & Disease Volume: 8 Issue: 2 Pages: e2621-e2621
  • DOI: 10.1038/cddis.2017.50
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] REP1 inhibits FOXO3-mediated apoptosis to promote cancer cell survival. (2017)
  • Author(s): Song KH, Woo SR, Chung JY, Lee HJ, Oh SJ, Hong SO, Shim J, Kim YN, Rho SB, Hong SM, Cho H, Hibi M, Bae DJ, Kim SY, Kim MG, Kim TW, Bae YK.
  • Journal Title: Cell Death & Disease Volume: 8 Issue: 1 Pages: e2536-e2536
  • DOI: 10.1038/cddis.2016.462
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Gene expression profiling of granule cells and Purkinje cells in the zebrafish cerebellum. (2017)
  • Author(s): Takeuchi M, Yamaguchi S, Sakakibara Y, Hayashi T, Matsuda K, Hara Y, Tanegashima C, Shimizu T, Kuraku S, Hibi M.
  • Journal Title: Journal of Comparative Neurology Volume: 525 Issue: 7 Pages: 1558-1585
  • DOI: 10.1002/cne.24114
  • NAID: 120006369328
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Osteocrin, a secretory peptide from heart, contributes to cranial osteogenesis in zebrafish (2016)
  • Author(s): Chiba A, Watanabe-Takano H, Terai K, Fukui H, Miyazaki T, Uemura M, Hashimoto H, Hibi M, Fukuhara S, Mochizuki N
  • Journal Title: Development Volume: 144 Pages: 334-344
  • DOI: 10.1242/dev.143354
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Responses of cerebellar Purkinje cells during fictive optomotor behavior in larval zebrafish. (2016)
  • Author(s): Scalise K, Shimizu T, Hibi M, Sawtell NB.
  • Journal Title: Journal of Neurophysiology Volume: 116 Issue: 5 Pages: 2067-2080
  • DOI: 10.1152/jn.00042.2016
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] ype IV collagen controls the axogenesis of cereberr granule cells by regulating basement membrane integrity in zebrafish. (2015)
  • Author(s): Takeuchi, M., Yamaguchi, S., Yonemura, S., Kakiguchi, K., Sato, Y., Higashiyama, T., Shimizu, T., and, Hibi, M.
  • Journal Title: PLoS genet. Volume: 11 Issue: 10 Pages: e1005587-e1005587
  • DOI: 10.1371/journal.pgen.1005587
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] PRMT8 as a phospholipase regulates Purkinje cell dendritic arborization and motor coordination. (2015)
  • Author(s): Kim, J.D., Park, K.E., Ishida, J., Kako, K., Hamada, J., Kani, S., Takeuchi, M., Namiki, K., Fukui, H., Fukuhara, S., Hibi, M,. Kobayashi, M., Kanaho, Y., Kasuya, Y., Mochizuki, N., Fukamizu, A.
  • Journal Title: Sci. Adv. Volume: 1 Issue: 11
  • DOI: 10.1126/sciadv.1500615
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Roles of cerebellar neural circuits in classical fear conditioning. (2017)
  • Author(s): Hibi M, Matsuda K, Yoshida M, Kawakami K, Shimizu T.
  • Organizer: International Workshop on Zebrafish Neural Circuits and Behavior.
  • Int'l Joint Research
• [Presentation] Formation and function of cerebellar neural circuits in zebrafish. (2017)
  • Author(s): Hibi M, Takeuchi M, Matsuda K, Ito T, Nimura T, Hara Y, Kuraku S, Kawakami K, Yoshida M, Shimizu T.
  • Organizer: 第23回小型魚類研究会
  • Invited
• [Presentation] Cerebellar neural circuitry is involved in the classical fear conditioning in zebrafish. (2017)
  • Author(s): Matsuda K, Yoshida M, Kawakami K, Hibi M, Shimizu T.
  • Organizer: 第2回モナッシュ大学脳科学研究所－富山大学理学部国際シンポジウム「神経行動学の最新動向」
  • Int'l Joint Research
• [Presentation] Transcriptome and functional analyses of genes expressed in cerebellar granule cells in zebrafish. (2017)
  • Author(s): Takeuchi M, Yamaguchi S, Sakakibara Y, Hayashi T, Matsuda K, Hara Y, Hayashi T, Kuraku S, Shimizu T, Hibi M
  • Organizer: 第23回小型魚類研究会
• [Presentation] The cerebellar granule cells control the recovery from classical conditioned fear responses in zebrafish. (2017)
  • Author(s): Shimizu T, Matsuda K, Yoshida M, Kawakami K, Hibi M.
  • Organizer: 第40回日本神経科学大会
• [Presentation] Roles of Ptf1a and Gsx2 in development of inferior olive nucleus neurons in zebrafish. (2017)
  • Author(s): Ito T, Takeuchi M, Sakagami M, Asakawa K, Kawakami K., Shimizu T, Hibi M.
  • Organizer: 第50回日本発生生物学会大会
• [Presentation] Reelin signaling is involved in layer and neural circuit formation in the cerebellum and the optic tectum in zebrafish. (2017)
  • Author(s): Nimura T, Di Donato V, Hayashi T, Takeuchi M, Shimizu T, Del Bene F, Hibi M.
  • Organizer: 第50回日本発生生物学会大会
• [Presentation] How did the weakly electric mormyrid fish Gnathonemus petersii evolve a large and foliated cerebellum? (2017)
  • Author(s): Matsuda K, Sakakibara Y, Hara Y, Kuraku S, Shimizu T, Hibi M.
  • Organizer: 第50回日本発生生物学会大会
• [Presentation] 真骨魚類から見た小脳の進化と発生 (2016)
  • Author(s): 日比正彦、竹内未紀、松田光司、原雄一郎、榊原考将、種子島千春、山口信悟、吉田将之、工樂樹洋、清水貴史
  • Organizer: 日本進化学会第18回大会
  • Place of Presentation: 東京
  • Year and Date: 2016-08-25
  • Invited
• [Presentation] Role of Contactin1 in neural network formation for motor coordination in medaka and zebrafish. (2016)
  • Author(s): Takeuchi M, Goshima A, Inoue C, Shimizu K, Kawahara A, Yoshida M, Hibi M.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜、神奈川
  • Year and Date: 2016-07-20
• [Presentation] Zebrafish cerebellar neural circuitry is involved in the classical fear conditioning. (2016)
  • Author(s): Matsuda K, Yoshida M, Kawakami K, Hibi M, Shimizu T.
  • Organizer: 第39回日本神経科学大会
  • Place of Presentation: 横浜、神奈川
  • Year and Date: 2016-07-20
• [Presentation] 真骨魚類に見る小脳の進化と発生 (2016)
  • Author(s): 日比正彦、竹内未紀、山口信悟、松田光司、原雄一郎、榊原考将、工樂樹洋、吉田将之、清水貴史
  • Organizer: 第121回日本解剖学会総会
  • Place of Presentation: 郡山市、福島
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] Roles of zebrafish cerebellar neural circuitry in classical fear conditioning. (2015)
  • Author(s): Matsuda K, Yoshida M, Asakawa K, Ohkura M, Nakai J, Kawakami K, Hibi M, Shimizu T.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸市、兵庫
  • Year and Date: 2015-07-28
• [Presentation] A nuclear protein Cfdp1 regulates differentiateon of granule cells in zebrafish cerebellum. (2015)
  • Author(s): Shimizu T, Kani S, Bae YK, Sun X, Hibi, M.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸市、兵庫
  • Year and Date: 2015-07-28
• [Presentation] Transcriptome analysis of granule cells and Purkinje cells in zebrafish cerebellum. (2015)
  • Author(s): Takeuchi M, Yamaguchi S, Hayashi T, Sakakibara Y, Matsuda K, Hara Y, Hayashi T, Kuraku S, Shimizu T, Hibi M.
  • Organizer: 第38回日本神経科学大会
  • Place of Presentation: 神戸市、兵庫
  • Year and Date: 2015-07-28
• [Presentation] Evolution and development of cerebellar neural circuitry in teleosts. (2015)
  • Author(s): Hibi M, Takeuchi M, Yamaguchi S, Matsuda K, Hayashi T, Hara Y, Hayashi T, Sakakibara Y, Yoshida M, Kuraku S, Shimizu M.
  • Organizer: 第48回日本発生生物学会大会
  • Place of Presentation: つくば市、茨城
  • Year and Date: 2015-06-02
• [Presentation] Integrity of basement membrane is important for axogenesis of cerebellar granule cells. (2015)
  • Author(s): Takeuchi M, Yamaguchi S, Hayashi T, Yonemura S, Hara Y, Hayashi T, Kuraku S, Shimizu T, Hibi M.
  • Organizer: 第48回日本発生生物学会大会
  • Place of Presentation: つくば市、茨城
  • Year and Date: 2015-06-02
• [Presentation] A nuclear protein Cfdp1 regulates differentiateon of granule cells in zebrafish cerebellum. (2015)
  • Author(s): Shimizu T, Kani S, Bae YK, Sun X, and Hibi M.
  • Organizer: 第48回日本発生生物学会大会
  • Place of Presentation: つくば市、茨城
  • Year and Date: 2015-06-02
• [Presentation] Formation and function of cerebellar neural circuitry. (2015)
  • Author(s): Hibi M.
  • Organizer: Zebrafish Systems Biology Workshop
  • Place of Presentation: Ashburn, Virginia, USA
  • Year and Date: 2015-04-23
  • Int'l Joint Research / Invited