Mechanisms regulating spatial patterning of dendrites by environmental sensing

• Project/Area Number: 16K18363
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurophysiology / General neuroscience
• 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): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 神経回路 / プルキンエ細胞 / フィロポディア / アクチン骨格 / 樹状突起 / 形態形成 / 樹状突起形成 / Mtss1 / 小脳プルキンエ細胞 / 樹状突起フィロポディア / 神経発生 / 発生・分化 / 神経科学 / 細胞・組織

Outline of Final Research Achievements

Cerebellar Purkinje cells construct their characteristic dendrites during development. Their dendritic filopodia sense the environmental cues and modify their growth dynamics to attain their appropriate shapes. We attempted to clarify the mechanisms controlling the dynamics from two points of view.　(1) The dendrites recognize the contact between dendritic arbors and eliminate the arbor to avoid excess crossing. We found that actin-regulator Mtss1 regulates the filopodial length and modify the frequency of contact between dendritic branches. We further demonstrated the mechanisms of how Mtss1 control the actin polymerization to modify filopodial length.　(2) The dendrites recognize the parallel fiber to control their dendrite growth orientation. The dendrites grow perpendicular to parallel fibers. We performed time-lapse imaging of dendrite growth during perpendicular growth to understand the mechanisms and attempted to identify the molecule to be involved in the recognition.

Academic Significance and Societal Importance of the Research Achievements

本研究では小脳プルキンエ細胞をモデルとし、ニューロンが発生期において組織内環境を認識しながら適切な形態を獲得する仕組みの解析を行った。樹状突起が固有の空間配置を獲得する上で、フィロポディアによる環境認識が一定の役割を果たすことを示した。本研究によって得られた知見は、哺乳類の神経回路形成メカニズムを理解する上で重要なものであり、将来的には発生不全に伴う神経疾患などの発症メカニズムへ貢献する可能性がある。

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
• [Journal Article] MTSS1 Regulation of Actin-Nucleating Formin DAAM1 in Dendritic Filopodia Determines Final Dendritic Configuration of Purkinje Cells (2018)
  • Author(s): Kawabata Galbraith Kelly、Fujishima Kazuto、Mizuno Hiroaki、Lee Sung-Jin、Uemura Takeshi、Sakimura Kenji、Mishina Masayoshi、Watanabe Naoki、Kengaku Mineko
  • Journal Title: Cell Reports Volume: 24 Issue: 1 Pages: 95-106
  • DOI: 10.1016/j.celrep.2018.06.013
  • NAID: 120006489939
  • Peer Reviewed / Open Access
• [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
• [Presentation] Fine-tuning of actin nucleator activity by MTSS1 in dendritic prtrusions of developing Purkinje Cells (2017)
  • Author(s): Kelly Kawabata, Kazuto Fujishima, Naoya Hino, Mineko Kengaku
  • Organizer: 日本神経科学大会