Elucidation of the significance of WNT/beta-Catenin signaling in adult zebrafish cardiomyocytes

• Project/Area Number: 18K15025
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: Chiba Ayano 国立研究開発法人国立循環器病研究センター, 研究所, 上級研究員 (10794159)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: WNT/βカテニンシグナル / 心筋細胞 / 冠血管 / ゼブラフィッシュ / 房室管 / 心拍 / WNT/βカテニン / 心臓発生 / 心臓機能

Outline of Final Research Achievements

Although the canonical Wnt/beta-catenin signaling activation in cardiomyocytes (CMs) is required for cardiac development including heart tube looping and atrioventricular valve formation, the role of the Wnt/beta-catenin signaling in the adult heart is not known. We developed transgenic zebrafish lines that visualize beta-catenin dependent transcriptional activation in CMs. Wnt/beta-catenin signaling was activated in CMs at the atrioventricular canal region from embryo to adult fish. We focused on the significance of Wnt/beta-catenin signaling activation in adult CMs.
We found that heartbeat-dependent Wnt expression activates Wnt/beta-catenin signaling in CMs at the AVC. We also identified that Wnt/beta-catenin signaling-activated CMs promote coronary vessel outgrowth.

Academic Significance and Societal Importance of the Research Achievements

心臓再生が可能であるゼブラフィッシュの冠血管形成メカニズムの解明は、発生学研究だけでなく、心臓再生研究でも重要な課題である。ゼブラフィッシュの冠血管は生後1ヶ月以降に房室管領域の心内膜内皮細胞から形成されるが、なぜ房室管から形成されるかは明らかになっていない。本研究によって、WNT/βカテニンシグナルを活性化心筋細胞による、新たな冠血管形成調節機構の存在が示唆された。房室管でのWNT/βカテニンシグナルの活性化は、冠血管が房室管から形成される理由の一つとなる可能性がある。

Research Products

• [Journal Article] Peri-arterial specification of vascular mural cells from na?ve mesenchyme requires Notch signaling (2019)
  • Author(s): Ando Koji、Wang Weili、Peng Di、Chiba Ayano、Lagendijk Anne K.、Barske Lindsey、Crump J. Gage、Stainier Didier Y. R.、Lendahl Urban、Koltowska Katarzyna、Hogan Benjamin M.、Fukuhara Shigetomo、Mochizuki Naoki、Betsholtz Christer
  • Journal Title: Development Volume: 146 Pages: 165589-165589
  • DOI: 10.1242/dev.165589
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] In vivoanalysis of cardiomyocyte proliferation during trabeculation (2018)
  • Author(s): Uribe Veronica、Ramadass Radhan、Dogra Deepika、Rasouli S. Javad、Gunawan Felix、Nakajima Hiroyuki、Chiba Ayano、Reischauer Sven、Mochizuki Naoki、Stainier Didier Y. R.
  • Journal Title: Development Volume: 145 Issue: 14
  • DOI: 10.1242/dev.164194
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Myocardial canonical Wnt signaling in zebrafish coronary vessel development (2019)
  • Author(s): Ayano Chiba, Naoki Mochizuki
  • Organizer: The 3rd JCS Council Forum on Basic CardioVascular Research
• [Presentation] Myocardial canonical Wnt signaling pathway regulates coronary vessel formation in zebrafish (2019)
  • Author(s): Ayano Chiba, Naoki Mochizuki
  • Organizer: Inaugural Joint Scientific Meeting of AVBS | ANZMS | AAVBM
  • Int'l Joint Research
• [Presentation] Wnt/βカテニンシグナル活性化心筋細胞は ゼブラフィッシュの冠血管の伸展を促進する (2019)
  • Author(s): 千葉彩乃、望月直樹
  • Organizer: 第42回 日本分子生物学会年会
• [Presentation] Wnt/β-cateninシグナル活性化心筋細胞がゼブラフィッシュ心臓発生に果たす役割 (2019)
  • Author(s): 千葉彩乃
  • Organizer: Wnt研究会2018-9/大阪大学蛋白研セミナー
• [Presentation] Wnt signaling-activated cardiomyocytes during cardiac development in zebrafish (2018)
  • Author(s): Ayano Chiba, Naoki Mochizuki
  • Organizer: Weinstein 2018
  • Int'l Joint Research
• [Presentation] Myocardial canonical Wnt signaling during cardiac development in zebrafish (2018)
  • Author(s): Ayano Chiba, Naoki Mochizuki
  • Organizer: International Vascular Biology Meeting 2018
  • Int'l Joint Research
• [Presentation] Endocardial and Myocardial canonical Wnt signaling in the developing zebrafish heart (2018)
  • Author(s): Ayano Chiba, Naoki Mochizuki
  • Organizer: The 16th Korea-Japan Joint Symposium on Vascular Biology（K-J meeting）
  • Int'l Joint Research
• [Presentation] Myocardial canonical Wnt signaling in zebrafish heart development (2018)
  • Author(s): Ayano Chiba, Naoki Mochizuki
  • Organizer: The 2nd JCS Council Forum on Basic CardioVascular Research
• [Book] Hormonal Signaling in Biology and Medicine (2019)
  • Author(s): Max Herbert Cake, George Yeoh, Sonia Lobo, John Arnott, Gabor Halmos, Nikoletta Dobos, Eva Juhasz, Asuzsanna Szabo, Ayano Chiba, Naoki Mochizuki, Gerald Litwack 他
  • Total Pages: 738
  • Publisher: Academic Press
  • ISBN: 9780128138144