Establishment of cerebellar connectome

• Project/Area Number: 24370088
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• 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)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000); Fiscal Year 2012: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
• Keywords: 小脳 / 神経回路形成 / ゼブラフィッシュ / 蛍光タンパク質 / 可視化 / ライブイメージング / 変異体 / 神経発生

Outline of Final Research Achievements

We isolated transgenic zebrafish lines that express a modified version of Gal4 in the cerebellar neural circuits: granule, Purkinje, eurydendroid cells, Bergmann glia, and or the neurons in the inferior olive nuclei. Using these lines, we investigated the anatomy and developmental processes of the cerebellar neural circuitry. Identification of the locus of the zebrafish mutant shiomaneki, which displays aberrant axons of granule cells, revealed that type IV collagen controls the formation of granule cell axons by regulating the integrity of the basement membrane. Analysis of the medaka mutant ro, which shows abnormal swimming behavior, revealed that Contactin1 plays a conserved role in the formation and/or function of the neural network involved in motor coordination. We carried out transcriptome analysis of cerebellar neurons to identify molecules controlling the cerebellar neural circuit formation.

Research Products

• [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
• [Journal Article] Establishment of Gal4 transgenic zebrafish lines for analysis of development of cerebellar neural circuitry (2015)
  • Author(s): Takeuchi, M., Matsuda, K., Yamaguchi, S., Asakawa, K., Miyasaka, N., Lal, P., Yoshihara, Y., Koga, A., Kawakami, K., Shimizu, T., and Hibi, M.
  • Journal Title: Developmental Biology Volume: 397 Issue: 1 Pages: 1-17
  • DOI: 10.1016/j.ydbio.2014.09.030
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sox5 functions as a fate switch in medaka pigment cell development. (2014)
  • Author(s): Nagao Y, Suzuki T, Shimizu A, Kimura T, Seki R, Adachi T, Inoue C, Omae Y, Kamei Y, Hara I, Taniguchi Y, Naruse K, Wakamatsu Y, Kelsh RN, Hibi M, Hashimoto H
  • Journal Title: PLoS genetics Volume: 10(4) Issue: 4 Pages: e1004246-e1004246
  • DOI: 10.1371/journal.pgen.1004246
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The parallel growth of motoneuron axons with the dorsal aorta depends on Vegfc/Vegfr3 signaling in zebrafish (2013)
  • Author(s): Kwon HB, Fukuhara S, Asakawa K, Ando K, Kashiwada T, Kawakami K Hibi M, Kwon YG, Kim KW, Alitalo K, Mochizuki N.
  • Journal Title: Development Volume: 140 Issue: 19 Pages: 4081-4090
  • DOI: 10.1242/dev.091702
  • Peer Reviewed
• [Journal Article] Requirement of zebrafish ataxin-7 in differentiation of photoreceptors and cerebellar neurons. (2012)
  • Author(s): Yanicostas, C.
  • Journal Title: PLoS One Volume: 7 Issue: 11 Pages: e50705-e50705
  • DOI: 10.1371/journal.pone.0050705
  • Peer Reviewed
• [Journal Article] Dynamic microtubules at the vegetal cortex predict the embryonic axis in zebrafish. (2012)
  • Author(s): Tran, L.D.
  • Journal Title: Development Volume: 139 Issue: 19 Pages: 3644-3652
  • DOI: 10.1242/dev.082362
  • Peer Reviewed
• [Journal Article] Lesion-induced generation of interneuron cell types in specific dorso-ventral domains in the spinal cord of adult zebrafish (2012)
  • Author(s): Kuscha, V., Fraser, S. L., Dias, T. B., Hibi, M., Becker, T., and Becker, C. G.
  • Journal Title: J. Comp. Neurol Volume: (in press) Issue: 16 Pages: 3604-3616
  • DOI: 10.1002/cne.23115
  • Peer Reviewed
• [Journal Article] The medaka zic1/zic4 mutant provides molecular insights into teleost caudal fin evolution. (2012)
  • Author(s): Yuuta Moriyama
  • Journal Title: Current Biology Volume: 21 Issue: 7 Pages: 601-607
  • DOI: 10.1016/j.cub.2012.01.063
  • Peer Reviewed
• [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・全国学術集会
  • Place of Presentation: 郡山
  • Year and Date: 2016-03-28
  • Invited
• [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
  • 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 T.
  • Organizer: 第48回日本発生生物学会大会
  • Place of Presentation: つくば
  • 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
  • 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: Jaenlia Research Campus, Virginia
  • Year and Date: 2015-04-22
  • Int'l Joint Research / Invited
• [Presentation] Precise assembly of the basement membrane is important for the axogenesis of cerebellar granule cells. (2014)
  • Author(s): Takeuchi M, Yamaguchi S, Yonemura S, Asakawa K, Kawakami K, Takada S, Shimizu T, Hibi M.
  • Organizer: 第20回小型魚類研究会
  • Place of Presentation: 東京
  • Year and Date: 2014-09-20 – 2014-09-21
• [Presentation] Basement membrane structure is important for axogenesis of cerebellar granule cells. (2014)
  • Author(s): Takeuchi M, Yonemura S, Asakawa K, Kawakami K, Takada S, Kuraku S, Hayashi T, Yamaguchi S, Shimizu T, Hibi M.
  • Organizer: 第37回日本神経科学大会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Control of axon guidance of cerebellar granule cells by the basement membrane. (2014)
  • Author(s): Takeuchi M, Hayashi T, Yamaguchi S, Yonemura S, Asakawa K, Kawakami K, Takada S, Kuraku S, Shimizu T, Hibi M.
  • Organizer: 11th International Conference on Zebrafish Development and Genetics
  • Place of Presentation: Wisconsin, USA
  • Year and Date: 2014-06-24 – 2014-06-28
• [Presentation] Dissection of cerebellar neural circuitry with zebrafish Gal4 gene/enhancer trap lines. (2014)
  • Author(s): Matsuda K, Takeuchi M, Asakawa K, Ohkura M, Miyasaka N, Yoshihara Y, Hayashi T, Kuraku S, Kawakami K, Hibi M, Shimizu T.
  • Organizer: 第47回日本発生生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-05-27 – 2014-05-30
• [Presentation] Precise axogenesis of the cerebellar granule cells requires interaction between their axons and the basement membrane. (2014)
  • Author(s): Takeuchi M, Yonemura S, Asakawa K, Kawakami K, Takada S, Shimizu T, Hibi M.
  • Organizer: 第47回日本発生生物学会大会
  • Place of Presentation: 名古屋
  • Year and Date: 2014-05-27 – 2014-05-30
• [Presentation] Microtubule-Dependent Dorsal Determination in zebrafish. (2013)
  • Author(s): 日比 正彦
  • Organizer: CDB symposium 2013
  • Place of Presentation: 理化学研究所(兵庫県)(招待講演)
  • Year and Date: 2013-03-05
• [Presentation] Development of cerebellar granule cell axons in zebrafish. (2013)
  • Author(s): Yamaguchi S, Takeuchi M, Asakawa K, Kawakami K, Shimizu T, and Hibi M.
  • Organizer: 第46回日本発生生物学会大会
  • Place of Presentation: 松江
• [Presentation] Basement membrane integrity is required for axogenesis of cerebellar granule cells. (2013)
  • Author(s): Takeuchi M, Yonemura S, Asakawa K, Kawakami K, Takada S, Shimizu T, Hibi M.
  • Organizer: 第46回日本発生生物学会大会
  • Place of Presentation: 松江
• [Presentation] 真骨魚類における小脳神経回路形成 (2012)
  • Author(s): 日比 正彦
  • Organizer: 総合研究大学院大学融合「脳の進化」研究会
  • Place of Presentation: 総合研究大学院大学(神奈川県)(招待講演)
  • Year and Date: 2012-11-13
• [Presentation] Formation of cerebellar neural circuits in zebrafish. (2012)
  • Author(s): 日比 正彦
  • Organizer: Swiss-Japanese Developmental Biology Meeting
  • Place of Presentation: 京都ガーデンパレス(京都府)
  • Year and Date: 2012-11-05
• [Presentation] Genetic control for neural circuit formation in teleost cerebellum. (2012)
  • Author(s): 日比 正彦
  • Organizer: 第45回日本発生生物学会合同大会
  • Place of Presentation: 神戸国際会議場(兵庫県)(招待講演)
  • Year and Date: 2012-05-31
• [Presentation] Role of basement membrane in axogenesis of cerebellar granule cells in zebrafish (2012)
  • Author(s): 日比 正彦
  • Organizer: Asia-Pacific Developmental Biology Conference
  • Place of Presentation: 台北(台湾)
• [Presentation] Deciphering cerebellar neural circuitry using the zebrafish model.
  • Author(s): Hibi M, Takeuchi M, Yamaguchi S, Matsuda K, Yonemura S, Asakawa K, Kawakami K, and Shimizu T.
  • Organizer: 高等研プロジェクト会議「ゲノム工学とイメージングサイエンスに基づく生命システム研究の新展開」
  • Place of Presentation: 京都
• [Presentation] Development of functional cerebellar neural circuitry in zebrafish.
  • Author(s): Hibi M, Takeuchi M, Yamaguchi S, Matsuda K, Yonemura S, Asakawa K, Kawakami K, and Shimizu T.
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
• [Presentation] Development of cerebellar neural circuitry.
  • Author(s): Hibi M.
  • Organizer: Janelia Workshop on Zebrafish Genetics, Transgenesis, and Systems Biology
  • Place of Presentation: Ashburn, VA, USA
  • Invited
• [Book] "Deciphering Cerebellar Neural Circuitry Involved in Higher Order Functions" in New Principles in Developmental Processes. (2014)
  • Author(s): Hibi M, Shimizu T.
  • Total Pages: 24
  • Publisher: Springer
• [Book] New Principles in Developmental Processes, Chapter 13 Deciphering Cerebellar Neural Circuitry Involved in Higher Order Functions Using the Zebrafish Model (2014)
  • Author(s): Hibi M, Shimizu T.
  • Publisher: Springer
• [Remarks] 名古屋大学生物機能開発利用研究センター動物器官機能研究分野
  • URL: http://bbc.agr.nagoya-u.ac.jp/~junkei/