Molecular mechanisms underlying the generation and transduction of mechanical forces during brain development

2021 Fiscal Year Final Research Report

• Project Area: Interplay of developmental clock and extracellular environment in brain formation
• Project/Area Number: 16H06484
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: Kengaku Mineko 京都大学, 高等研究院, 教授 (10303801)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: 発生・分化 / 細胞・組織 / 脳・神経

Outline of Final Research Achievements

We analyzed the impact of the mechanical properties of the developing brain tissue and cells in the control of the fate, position and shape of neurons in the well-organized cortex. We found that neurons switch the actomyosin force generation mechanisms in response to the mechanical stress of the surrounding microenvironment. We also found that the nuclei of newborn neurons are extremely soft due to its special nuclear lamina structure. The soft nucleus squeeze into the narrow tissue spaces against the shear stress by sharp deformation and rotation driven by the dynamic force of microtubule motors. We also proved that dendritic filopodia act as mechanosensors for space exploration and control the spatial distribution of dendritic arbors where collisions between projections do not occur. Furthermore, we developed a gel substrate that reproduces the softness of brain tissue and established a protocol to promote neuronal differentiation from neural stem cells.

Free Research Field

神経発生学

Academic Significance and Societal Importance of the Research Achievements

これまでの脳発生研究は、化学シグナルの連鎖によるプログラムの進行と捉えられてきた。本研究は、ニューロンや脳組織の物理的な性質による空間的束縛の影響下で、脳皮質発生を担うニューロン細胞運動が効果的に駆動される力学的制御機構の一端を明らかにした点で、脳皮質構築の形成機構の理解にブレークスルーをもたらしたと考える。また、ニューロンの力学的性質を計測する微小力学計測技術を確立し、緻密な細胞配向と突起空間分布の再現が不可欠な脳組織のin vitro３Ｄ再構築の基盤技術に発展した。今後器質的に損傷した脳の再生医療分野に貢献できる可能性がある。