Elucidation of mechanical stress response mechanism using imaging analysis of genetically modified zebrafish

2023 Fiscal Year Final Research Report

• Project/Area Number: 19KK0233
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research (B))
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 57:Oral science and related fields
• Research Institution: Showa University
• Principal Investigator: Chatani Masahiro 昭和大学, 歯学部, 准教授 (80628628)
• Project Period (FY): 2019-10-07 – 2024-03-31
• Keywords: ゼブラフィッシュ / メダカ / 骨 / 血管 / 血球細胞

Outline of Final Research Achievements

We focused on the cloche zebrafish mutant. We generated npas4l gene-deficient medaka to elucidate the mechanism conserved across species. The npas4l-deficient medaka exhibited a marked decrease in hematopoietic and vascular endothelial cells. Single-cell RNA-seq analysis identified a cell population expressing both hematopoietic and vascular endothelial cell markers, and gene expression analysis suggested that hemangioblasts were localized around the early embryo. In addition, dysplasia of some bones was observed, suggesting the involvement of blood vessels in hard tissue formation. The enhancers that function during fin regeneration in zebrafish were analyzed in medaka, and an enhancer that is strongly expressed during fin regeneration in medaka was identified. It is expected to elucidate the mechanism of hard tissue regeneration that is conserved across species.

Free Research Field

骨生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で小型魚類を用いることで血球と血管の両者に共通な前駆細胞である血球血管芽細胞の存在を示唆し、それに関する遺伝子発現のデータベースを構築できた点で学術的意義がある。また血管、血球、一部の骨を欠失した変異体を作出しており、その解析から生体内メカニカルストレスの受容メカニズム解明が期待される。血球血管芽細胞はヒトにも存在する幹細胞と考えられており、その分化メカニズム解明により関連疾患の解決が期待されるという点で社会的意義がある。種を超えて保存されている、組織の再生に重要なエンハンサー領域を明らかにすることは、再生医学においても重要な課題であり、将来的に再生医療への貢献が期待される。