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Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling
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 ro...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794269/ https://www.ncbi.nlm.nih.gov/pubmed/35030171 http://dx.doi.org/10.1371/journal.pbio.3001505 |
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author | Chow, Renee Wei-Yan Fukui, Hajime Chan, Wei Xuan Tan, Kok Soon Justin Roth, Stéphane Duchemin, Anne-Laure Messaddeq, Nadia Nakajima, Hiroyuki Liu, Fei Faggianelli-Conrozier, Nathalie Klymchenko, Andrey S. Choon Hwai, Yap Mochizuki, Naoki Vermot, Julien |
author_facet | Chow, Renee Wei-Yan Fukui, Hajime Chan, Wei Xuan Tan, Kok Soon Justin Roth, Stéphane Duchemin, Anne-Laure Messaddeq, Nadia Nakajima, Hiroyuki Liu, Fei Faggianelli-Conrozier, Nathalie Klymchenko, Andrey S. Choon Hwai, Yap Mochizuki, Naoki Vermot, Julien |
author_sort | Chow, Renee Wei-Yan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8794269 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-87942692022-01-28 Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling Chow, Renee Wei-Yan Fukui, Hajime Chan, Wei Xuan Tan, Kok Soon Justin Roth, Stéphane Duchemin, Anne-Laure Messaddeq, Nadia Nakajima, Hiroyuki Liu, Fei Faggianelli-Conrozier, Nathalie Klymchenko, Andrey S. Choon Hwai, Yap Mochizuki, Naoki Vermot, Julien PLoS Biol Research Article 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. Public Library of Science 2022-01-14 /pmc/articles/PMC8794269/ /pubmed/35030171 http://dx.doi.org/10.1371/journal.pbio.3001505 Text en © 2022 Chow et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Chow, Renee Wei-Yan Fukui, Hajime Chan, Wei Xuan Tan, Kok Soon Justin Roth, Stéphane Duchemin, Anne-Laure Messaddeq, Nadia Nakajima, Hiroyuki Liu, Fei Faggianelli-Conrozier, Nathalie Klymchenko, Andrey S. Choon Hwai, Yap Mochizuki, Naoki Vermot, Julien Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling |
title | Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling |
title_full | Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling |
title_fullStr | Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling |
title_full_unstemmed | Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling |
title_short | Cardiac forces regulate zebrafish heart valve delamination by modulating Nfat signaling |
title_sort | cardiac forces regulate zebrafish heart valve delamination by modulating nfat signaling |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794269/ https://www.ncbi.nlm.nih.gov/pubmed/35030171 http://dx.doi.org/10.1371/journal.pbio.3001505 |
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