egr3 is a mechanosensitive transcription factor gene required for cardiac valve 
morphogenesis

Ribeiro da Silva, Agatha; Gunawan, Felix; Boezio, Giulia L. M.; Faure , Emilie; Theron  , Alexis; Avierinos , Jean-Francois; Lim, S; Shivam, Govind Jha; Ramadass, Radhan; Guenther, Stefan; Looso, Mario; Zaffran, Stephane; Juan, T; Stainier, Didier Y. R.

doi:10.1126/sciadv.adl0633

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis

MPS-Authors

/persons/resource/persons251594

Ribeiro da Silva, Agatha
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons228722

Gunawan, Felix
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons239402

Boezio, Giulia L. M.
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons290087

Lim, S
Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons299857

Shivam, Govind Jha
Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224268

Ramadass, Radhan
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224128

Guenther, Stefan
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224384

Looso, Mario
Bioinformatics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons289507

Juan, T
Max Planck Institute for Heart and Lung Research, Max Planck Society;

/persons/resource/persons224278

Stainier, Didier Y. R.
Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Ribeiro da Silva, A., Gunawan, F., Boezio, G. L. M., Faure, E., Theron, A., Avierinos, J.-F., et al. (2024). egr3 is a mechanosensitive transcription factor gene required for cardiac valve morphogenesis. SCIENCE ADVANCES, 10(20): eadl0633. doi:10.1126/sciadv.adl0633.

Cite as: https://hdl.handle.net/21.11116/0000-000F-84E2-C

Abstract

Biomechanical forces, and their molecular transducers, including key mechanosensitive transcription factor genes, such as KLF2, are required for cardiac valve morphogenesis. However, klf2 mutants fail to completely recapitulate the valveless phenotype observed under no-flow conditions. Here, we identify the transcription factor EGR3 as a conserved biomechanical force transducer critical for cardiac valve formation. We first show that egr3 null zebrafish display a complete and highly penetrant loss of valve leaflets, leading to severe blood regurgitation. Using tissue-specific loss- and gain-of-function tools, we find that during cardiac valve formation, Egr3 functions cell-autonomously in endothelial cells, and identify one of its effectors, the nuclear receptor Nr4a2b. We further find that mechanical forces up-regulate egr3/EGR3 expression in the developing zebrafish heart and in porcine valvular endothelial cells, as well as during human aortic valve remodeling. Altogether, these findings reveal that EGR3 is necessary to transduce the biomechanical cues required for zebrafish cardiac valve morphogenesis, and potentially for pathological aortic valve remodeling in humans.