PUBLICATION
Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling
- Authors
- Chow, R.W., Fukui, H., Chan, W.X., Tan, K.S.J., Roth, S., Duchemin, A.L., Messaddeq, N., Nakajima, H., Liu, F., Faggianelli-Conrozier, N., Klymchenko, A.S., Choon Hwai, Y., Mochizuki, N., Vermot, J.
- ID
- ZDB-PUB-220115-5
- Date
- 2022
- Source
- PLoS Biology 20: e3001505 (Journal)
- Registered Authors
- Fukui, Hajime, Mochizuki, Naoki, Nakajima, Hiroyuki, Roth, Stéphane, Vermot, Julien
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Embryo, Nonmammalian
- Endothelium
- Heart/embryology
- Heart Valves/abnormalities*
- Hemodynamics*
- Hemorheology
- Mechanical Phenomena
- Mesoderm
- NFATC Transcription Factors/genetics
- NFATC Transcription Factors/metabolism*
- Zebrafish/embryology*
- Zebrafish/genetics
- PubMed
- 35030171 Full text @ PLoS Biol.
Citation
Chow, R.W., Fukui, H., Chan, W.X., Tan, K.S.J., Roth, S., Duchemin, A.L., Messaddeq, N., Nakajima, H., Liu, F., Faggianelli-Conrozier, N., Klymchenko, A.S., Choon Hwai, Y., Mochizuki, N., Vermot, J. (2022) Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling. PLoS Biology. 20:e3001505.
Abstract
In the clinic, most cases of congenital heart valve defects are thought to arise through errors that occur after the endothelial-mesenchymal transition (EndoMT) stage of valve development. Although mechanical forces caused by heartbeat are essential modulators of cardiovascular development, their role in these later developmental events is poorly understood. To address this question, we used the zebrafish superior atrioventricular valve (AV) as a model. We found that cellularized cushions of the superior atrioventricular canal (AVC) morph into valve leaflets via mesenchymal-endothelial transition (MEndoT) and tissue sheet delamination. Defects in delamination result in thickened, hyperplastic valves, and reduced heart function. Mechanical, chemical, and genetic perturbation of cardiac forces showed that mechanical stimuli are important regulators of valve delamination. Mechanistically, we show that forces modulate Nfatc activity to control delamination. Together, our results establish the cellular and molecular signature of cardiac valve delamination in vivo and demonstrate the continuous regulatory role of mechanical forces and blood flow during valve formation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping