The molecular mechanism for cell fate determination and neural circuit formation of inferior olive nucleus neurons.

• Project/Area Number: 16K18548
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Developmental biology
• Research Institution: Nagoya University
• Principal Investigator: 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: ITO Tsubasa 名古屋大学
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 神経発生 / 神経分化 / 神経回路形成 / 転写因子 / 下オリーブ核 / ゼブラフィッシュ / 変異体 / 小脳 / 下オリーブ核ニューロン / gsx2 / ptf1a

Outline of Final Research Achievements

Purkinje cells in the cerebellum receive climbing fibers which originate from inferior olive nuclei (IOs) nuclei. The formation and patterning of the caudal rhombomeres (r) are controlled by gradients of fibroblast growth factor (Fgf) and retinoic acid (RA) signals: Fgf high at r4 vs. RA high at r7. The proneural gene ptf1a and the homeobox gene gsx2 are expressed in the ventricular zone of r7. The IO neurons are derived from the ptf1a+ gsx2+ progenitors in zebrafish. We established mutants for ptf1a and gsx2. Both mutant larvae showed reduction or loss of the IO neurons. The expression of ptf1a and gsx2 wasn’t affected in gsx2 and ptf1a mutants, respectively. Inhibition of the RA signal resulted in reduction of the gsx2 expression and the formation of the IO neurons. Our results indicate that (1) the RA signal controls expression of gsx2 that is involved in the formation of the IO neurons, (2) Ptf1a and Gsx2 cooperatively but independently regulate the formation of the IO neurons.

Research Products

• [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
• [Presentation] Gene expression profiling of zebrafish cerebellar neurons reveals possible mechanisms controlling neural circuit formation. (2017)
  • Author(s): Takeuchi M, Yamaguchi S, Sakakibara Y, Hayashi T, Matsuda K, Hara Y, Hayashi T, Kuraku S, Shimizu T, Hibi M.
  • Organizer: 日本発生生物学会
• [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: 小型魚類研究会
• [Presentation] ゼブラフィッシュのプルキンエ細胞および下オリーブ核ニューロンの発生を制御するPtf1aおよびGsx2の機能解析 (2016)
  • Author(s): 伊藤 翼
  • Organizer: 日本発生生物学会 秋季シンポジウム2016
  • Place of Presentation: 三島市民文化会館
  • Year and Date: 2016-10-19