PUBLICATION
The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression
- Authors
- Gentile, A., Bensimon-Brito, A., Priya, R., Maischein, H.M., Piesker, J., Guenther, S., Gunawan, F., Stainier, D.Y.
- ID
- ZDB-PUB-210622-50
- Date
- 2021
- Source
- eLIFE 10: (Journal)
- Registered Authors
- Bensimon-Brito, Anabela, Maischein, Hans-Martin, Stainier, Didier
- Keywords
- cardiac development, cell biology, cell extrusion, developmental biology, tissue integrity, zebrafish
- Datasets
- GEO:GSE162604
- MeSH Terms
-
- Animals
- Gene Expression Regulation*
- Heart/physiology*
- Intermediate Filaments/genetics*
- Myocardium/metabolism
- Snail Family Transcription Factors/genetics*
- Snail Family Transcription Factors/metabolism
- Zebrafish/genetics
- Zebrafish/physiology*
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 34152269 Full text @ Elife
Citation
Gentile, A., Bensimon-Brito, A., Priya, R., Maischein, H.M., Piesker, J., Guenther, S., Gunawan, F., Stainier, D.Y. (2021) The EMT transcription factor Snai1 maintains myocardial wall integrity by repressing intermediate filament gene expression. eLIFE. 10:.
Abstract
The transcription factor Snai1, a well-known regulator of epithelial-to-mesenchymal transition, has been implicated in early cardiac morphogenesis as well as in cardiac valve formation. However, a role for Snai1 in regulating other aspects of cardiac morphogenesis has not been reported. Using genetic, transcriptomic, and chimeric analyses in zebrafish, we find that Snai1b is required in cardiomyocytes for myocardial wall integrity. Loss of snai1b increases the frequency of cardiomyocyte extrusion away from the cardiac lumen. Extruding cardiomyocytes exhibit increased actomyosin contractility basally as revealed by enrichment of p-myosin and α-catenin epitope α-18, as well as disrupted intercellular junctions. Transcriptomic analysis of wild-type and snai1b mutant hearts revealed the dysregulation of intermediate filament genes, including desmin b (desmb) upregulation. Cardiomyocyte-specific desmb overexpression caused increased cardiomyocyte extrusion, recapitulating the snai1b mutant phenotype. Altogether, these results indicate that Snai1 maintains the integrity of the myocardial epithelium, at least in part by repressing desmb expression.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping