Elucidation of signal pathways that mechanically regulate direction-dependent collective cell motion essential for forebrain morphogenesis

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K18155
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 62010:Life, health and medical informatics-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Ohtsuka Daisuke 国立研究開発法人理化学研究所, 生命機能科学研究センター, 上級研究員 (40632865)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 形態形成 / 力学応答 / 細胞動態 / 4D計測

Outline of Final Research Achievements

Our previous studies have revealed that anisotropic tissue elongation by directional cell rearrangement is important for forebrain morphogenesis. Then, how are these directions determined? The purpose of this research is to clarify this. As a factor that determines the directionality, we hypothesized that SHH, which is a morphogen, and tissue stress derived from organ shape might be involved in the directionality determination. To verify this, we artificially applied an external force to tissue pieces taken from a developing neural tube. As a result, the tissue was elongated in the direction perpendicular to the external force through cell rearrangement. On the other hand, in the presence of SHH inhibitor, these responses did not appear and the tissue was hardly deformed. Taken together, we can conclude that SHH confers mechanical response on cells.

Free Research Field

発生生物学

Academic Significance and Societal Importance of the Research Achievements

本研究課題の達成は、正常発生過程の理解だけに止まらず、遺伝子異常による先天性奇形の理解にも繋がることが予想される。例えば、SHHシグナル経路の異常は全前脳胞症を引き起こす主要な原因の一つであることが明らかとなっている。これまで全前脳胞症の形態異常は正中組織の形成不全により起こっていることが想定されてきたが、申請者らの各階層動態の定量計測および解析により形態異常は応力検知能の異常による細胞集団運動方向の消失が原因であることが明らかとなった。このように方向性を持った細胞集団運動と形態異常がリンクすることはこれまで想定されていなかったため、治療法の開発等に関して新たな視点を提供できると考えられる。