Role of left atrium-restricted expression of Pitx2 in mouse heart development

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06203
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 44020:Developmental biology-related
• Research Institution: Toyo University
• Principal Investigator: Koshiba-Takeuchi Kazuko 東洋大学, 生命科学部, 教授 (30467005)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 心臓 / 発生 / 転写因子

Outline of Final Research Achievements

To understand the significance of left atrium-restricted expression of Pitx2 in mouse heart development, we generated mice in which Pitx2 is expressed throughout the heart. Pitx2-overexpressed mice were lethal at around embryonic day 12.5, and the formation of the atrioventricular canal was significantly altered. In addition, an atrial septal defect and impaired right atrial identity were caused. We performed single-cell RNA-sequencing to clarify the genes responsible for the phenotypes of Pitx2-overexpressing hearts in different cell types. As a result, we found that the expression of sinus node marker genes was reduced and the genes involved in extracellular matrix degradation and synthesis were altered in the myocardium.

Free Research Field

心臓発生

Academic Significance and Societal Importance of the Research Achievements

Pitx2は体軸の左右性形成に重要な転写因子であり、左側の側板中胚葉での発現が左心房特異的な発現へと維持される。Pitx2を機能阻害すると、心臓の低形成、房室管の異常、流出路の異常などが引き起こされることが報告されている。さらに、近年、不整脈との関連も明らかになっている。これまで、心臓発生におけるPitx2の機能解析は主に機能阻害を用いて行われており、過剰発現による解析はほとんど行われてこなかった。本研究から得られた成果は、心臓発生にはPitx2の適正な発現が重要であることを示し、また房室管形成に関与する新たな分子メカニズムの提唱につながる。