PT  - JOURNAL ARTICLE
AU  - Anne Laure Duchemin
AU  - Hélène Vignes
AU  - Julien Vermot
TI  - Mechanically activated Piezo channels control outflow tract valve development through Yap1 and Klf2-Notch signaling axis
AID  - 10.1101/529016
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 529016
4099  - http://biorxiv.org/content/early/2019/01/23/529016.short
4100  - http://biorxiv.org/content/early/2019/01/23/529016.full
AB  - 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 essential for regulating these pathways. In addition, live reporters reveal that piezo controls Klf2 and Notch activity in the endothelium and Yap1 expression 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.