PUBLICATION
klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis
- Authors
- Steed, E., Faggianelli, N., Roth, S., Ramspacher, C., Concordet, J.P., Vermot, J.
- ID
- ZDB-PUB-160526-6
- Date
- 2016
- Source
- Nature communications 7: 11646 (Journal)
- Registered Authors
- Faggianelli, Nathalie, Roth, Stéphane, Steed, Emily, Vermot, Julien
- Keywords
- Biological sciences, Cell biology, Developmental biology
- Datasets
- GEO:GSE79585
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Extracellular Matrix/metabolism
- Fibronectins/metabolism*
- Gene Expression Profiling
- Heart Valves/embryology*
- Kruppel-Like Transcription Factors/metabolism*
- Mechanotransduction, Cellular*
- Zebrafish
- Zebrafish Proteins/metabolism*
- PubMed
- 27221222 Full text @ Nat. Commun.
Citation
Steed, E., Faggianelli, N., Roth, S., Ramspacher, C., Concordet, J.P., Vermot, J. (2016) klf2a couples mechanotransduction and zebrafish valve morphogenesis through fibronectin synthesis. Nature communications. 7:11646.
Abstract
The heartbeat and blood flow signal to endocardial cell progenitors through mechanosensitive proteins that modulate the genetic program controlling heart valve morphogenesis. To date, the mechanism by which mechanical forces coordinate tissue morphogenesis is poorly understood. Here we use high-resolution imaging to uncover the coordinated cell behaviours leading to heart valve formation. We find that heart valves originate from progenitors located in the ventricle and atrium that generate the valve leaflets through a coordinated set of endocardial tissue movements. Gene profiling analyses and live imaging reveal that this reorganization is dependent on extracellular matrix proteins, in particular on the expression of fibronectin1b. We show that blood flow and klf2a, a major endocardial flow-responsive gene, control these cell behaviours and fibronectin1b synthesis. Our results uncover a unique multicellular layering process leading to leaflet formation and demonstrate that endocardial mechanotransduction and valve morphogenesis are coupled via cellular rearrangements mediated by fibronectin synthesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping