Mechanically activated Piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis
- Institut de Génétique et de Biologie Moléculaire et Cellulaire, France
Abstract
Mechanical forces are well known for modulating heart valve developmental programs. Yet, it is still unclear how genetic programs and mechanosensation interact during heart valve development. Here, we assessed the mechanosensitive pathways involved during zebrafish outflow tract (OFT) valve development in vivo. Our results show that the hippo effector Yap1, Klf2, and the Notch signaling pathway are all essential for OFT valve morphogenesis in response to mechanical forces, albeit active in different cell layers. Furthermore, we show that Piezo and TRP mechanosensitive channels are important factors modulating these pathways. In addition, live reporters reveal that Piezo controls Klf2 and Notch activity in the endothelium and Yap1 localization in the smooth muscle progenitors to coordinate OFT valve morphogenesis. Together, this work identifies a unique morphogenetic program during OFT valve formation and places Piezo as a central modulator of the cell response to forces in this process.
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Author details
Funding
H2020 European Research Council (682938 - EVALVE)
- Julien Vermot
Fondation pour la Recherche Médicale (DEQ29553)
- Julien Vermot
Agence Nationale de la Recherche (ANR-15-CE13-0015-01)
- Anne-Laure Duchemin
- Hélène Vignes
- Julien Vermot
European Molecular Biology Organization (Young Investigator Program)
- Julien Vermot
Fondation Lefoulon Delalande
- Anne-Laure Duchemin
Agence Nationale de la Recherche (ANR-10-IDEX-0002-02)
- Anne-Laure Duchemin
- Hélène Vignes
- Julien Vermot
Agence Nationale de la Recherche (ANR-12-ISV2-0001-01)
- Anne-Laure Duchemin
- Hélène Vignes
- Julien Vermot
Agence Nationale de la Recherche (ANR-10-LABX-0030-INRT)
- Anne-Laure Duchemin
- Hélène Vignes
- Julien Vermot
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were approved by the Animal Experimentation Committee of the Institutional Review Board of the IGBMC.(reference numbers MIN APAFIS#4669-2016032411093030 v4 and MIN4669-2016032411093030 v4-detail of entry 1).
Copyright
© 2019, Duchemin et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Mechanically activated Piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis
eLife 8:e44706.
https://doi.org/10.7554/eLife.44706
