PUBLICATION
The developing epicardium regulates cardiac chamber morphogenesis by promoting cardiomyocyte growth
- Authors
- Boezio, G.L.M., Zhao, S., Gollin, J., Priya, R., Mansingh, S., Guenther, S., Fukuda, N., Gunawan, F., Stainier, D.Y.R.
- ID
- ZDB-PUB-220930-6
- Date
- 2022
- Source
- Disease models & mechanisms 16(5): (Journal)
- Registered Authors
- Priya, Rashmi, Stainier, Didier
- Keywords
- Cardiomyocytes, Cell growth, Epicardium, Heart development, Inter-tissue crosstalk, Zebrafish
- Datasets
- GEO:GSE174505
- MeSH Terms
-
- Animals
- Heart/physiology
- Ligands
- Myocardium/metabolism
- Myocytes, Cardiac*/metabolism
- Organogenesis/genetics
- Pericardium/metabolism
- Transcription Factors/genetics
- Transcription Factors/metabolism
- Vascular Endothelial Growth Factor A/metabolism
- WT1 Proteins/genetics
- WT1 Proteins/metabolism
- Zebrafish*/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 36172839 Full text @ Dis. Model. Mech.
Citation
Boezio, G.L.M., Zhao, S., Gollin, J., Priya, R., Mansingh, S., Guenther, S., Fukuda, N., Gunawan, F., Stainier, D.Y.R. (2022) The developing epicardium regulates cardiac chamber morphogenesis by promoting cardiomyocyte growth. Disease models & mechanisms. 16(5):.
Abstract
The epicardium, the outermost layer of the heart, is an important regulator of cardiac regeneration. However, a detailed understanding of the crosstalk between the epicardium and myocardium during development requires further investigation. Here, we generated three models of epicardial impairment in zebrafish by mutating the transcription factor genes tcf21 and wt1a, and ablating tcf21+ epicardial cells. Notably, all three epicardial-impairment models exhibit smaller ventricles. We identified the initial cause of this phenotype as defective cardiomyocyte growth, resulting in reduced cell surface and volume. This failure of cardiomyocyte growth is followed by decreased proliferation and increased abluminal extrusion. By temporally manipulating its ablation, we show that the epicardium is required to support cardiomyocyte growth mainly during early cardiac morphogenesis. By transcriptomic profiling of sorted epicardial cells, we identified reduced expression of FGF and VEGF ligand genes in tcf21-/- hearts, and pharmacological inhibition of these signaling pathways partially recapitulated the ventricular growth defects. Altogether, these data further reveal the distinct roles of the epicardium during cardiac morphogenesis and the signaling pathways underlying epicardial-myocardial crosstalk.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping