Molecular and dynamic basis of axon guidance by mechanical stimulation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19453
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Neuroscience and related fields
• Research Institution: Kyoto University
• Principal Investigator: Kengaku MIneko 京都大学, 高等研究院, 教授 (10303801)
• Co-Investigator(Kenkyū-buntansha): 亀井 謙一郎 京都大学, 高等研究院, 准教授 (00588262)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 軸索ガイダンス / ナノパターン / メカノバイオロジー / 細胞密着

Outline of Final Research Achievements

We sought to identify a novel mechanism of axon guidance by mechanical properties of the developing brain tissue. Using nanoimprint lithography, we developed culture substrates with various line & space patterns and observed the growth of primary hippocampal and cerebellar neurons. We found that hippocampal neurons extend the axon perpendicularly to the narrow lines below 200 nm, while it runs along the thicker lines, indicating that axonal growth is influenced by the shape of extracellular substrates. Traction force microscopy revealed the generation of centripetal force at the periphery of extending growth cones. In contrast, actin fibers form random meshwork in the growth cones independently of the growth orientation as observed by scanning electron microscopy. Ongoing efforts to improve the patterned substrates with novel smart materials will clarify dynamic force generation during the oriented axonal elongation by confocal and TIRF microscopy.

Free Research Field

神経発生生物学

Academic Significance and Societal Importance of the Research Achievements

神経回路配線は遺伝的プログラムに従ったタンパク質情報で規定されるというパラダイムを超え、組織空間の機械的性質が軸索走行の制御に関わることが示唆された。また最新の生物工学、材料科学の技術を取り入れ、細胞の微小物理量を計測する新たな解析系の開発を行なった。これらの知見と技術を発展させれば、細胞自身のもつ力学的性質を利用して細胞運動を自在に誘導するスキャフォールドをデザインすることが可能となり、将来、器質的・機能的に損傷した脳部位への再生医療の基盤技術となることが期待される。