Cerebellar circuit formation mediated by the geometrical interaction between axon and dendrite

• Project/Area Number: 16KT0171
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Constructive Systems Biology
• Research Institution: Kyoto University
• Principal Investigator: Fujishima Kazuto 京都大学, 高等研究院, 特定助教 (20525852)
• Project Period (FY): 2016-07-19 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 小脳 / プルキンエ細胞 / 樹状突起 / スペクトリン / 神経回路形成 / 微小管 / 樹状突起形成 / 小脳回路 / 神経発生

Outline of Final Research Achievements

This study aimed to clarify the mechanisms regulating the autonomous neuronal circuit formation, especially focusing on the orthogonal interaction between Purkinje cell dendrites and granule cell axons in the cerebellar circuits. We showed that Spectrin beta III is essential for the perpendicular dendrite formation with respect to axonal fibers. The molecule forms regular periodic structures in the Purkinje cell dendrites and their filopodial base by using super-resolution microscopy STED. We also found that Spectrin beta III regulated the microtubule dynamics in the dendritic area. In the absence of Spectrin beta III, microtubule polymerized into the filopodial region more frequently than control, which resulted in the abnormal extension of filopodia in the wrong direction. Our results demonstrated that Spectrin beta III plays a pivotal role in the regulation of dendritic growth orientation during cerebellar circuit formation.

Academic Significance and Societal Importance of the Research Achievements

本研究により明らかになった知見は、軸索と樹状突起が協調して小脳神経回路形成を行う仕組みの一端を明らかにするものである。軸索と樹状突起が幾何学的に相互作用し、適切な回路を形成するというものでその仕組みはほとんど明らかにされていなかった。本研究で得られた結果は、哺乳類神経回路形成メカニズムを理解するうえで新たな考え方を提供する。また本研究で着目したSpectrin beta III は神経疾患の原因因子として知られており、今後の展開は疾患の発症メカニズムの理解に役立つ可能性がある。

Research Products

• [Journal Article] Dendritic Self-Avoidance and Morphological Development of Cerebellar Purkinje Cells (2019)
  • Author(s): Kazuto Fujishima, Kelly Kawabata Galbraith and Mineko Kengaku
  • Journal Title: The Cerebellum Volume: 17 Issue: 6 Pages: 701-708
  • DOI: 10.1007/s12311-018-0984-8
  • Peer Reviewed
• [Presentation] 小脳回路における軸索束依存的な樹状突起形成メカニズム (2018)
  • Author(s): 藤島和人
  • Organizer: 2018年度 生理学研究所研究会 「神経発達・再生研究会」
  • Invited
• [Presentation] Cytoskeletal control of the tree shape of neuronal dendrites in the brain (2018)
  • Author(s): Kazuto Fujishima
  • Organizer: 24th iCeMS International Symposium /Emerging Science for Unlocking Cell's Secrets
  • Int'l Joint Research / Invited
• [Presentation] Cellular and molecular mechanisms regulating dendrite directionality of cerebellar Purkinje cell (2018)
  • Author(s): Kazuto Fujishima and Mineko Kengaku
  • Organizer: The 41st Annual Meeting of the Japan Neuroscience Society
  • Invited
• [Presentation] Beta III Spectrin is required for the dendrite growth guided by axonal bundles in cerebellarc circuits. (2018)
  • Author(s): Kazuto Fujishima, Midori Yamada, Yukiko Nishida, Junko Kurisu and Mineko Kengaku
  • Organizer: 22nd Biennial Meeting of the International Society for Developmental Neuroscience
  • Int'l Joint Research
• [Presentation] 小脳回路における軸索束に依存した樹状突起形成メカニズム (2017)
  • Author(s): 藤島和人、山田緑、西田由貴子、栗栖純子、見学美根子
  • Organizer: 日本神経科学大会