PUBLICATION
Mechanically activated Piezo channels modulate outflow tract valve development through the Yap1 and Klf2-Notch signaling axis
- Authors
- Duchemin, A.L., Vignes, H., Vermot, J.
- ID
- ZDB-PUB-190917-1
- Date
- 2019
- Source
- eLIFE 8: (Journal)
- Registered Authors
- Duchemin, Anne-Laure, Vermot, Julien
- Keywords
- developmental biology, zebrafish
- MeSH Terms
-
- Stress, Mechanical*
- Signal Transduction*
- Trans-Activators/metabolism*
- Heart Valves/embryology*
- Ion Channels/metabolism*
- PubMed
- 31524599 Full text @ Elife
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.
Genes / Markers
Figure Gallery (9 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping