PUBLICATION
The E3 ubiquitin-protein ligase Rbx1 regulates cardiac wall morphogenesis in zebrafish
- Authors
- Sarvari, P., Rasouli, S.J., Allanki, S., Stone, O.A., Sokol, A., Graumann, J., Stainier, D.Y.R.
- ID
- ZDB-PUB-210808-13
- Date
- 2021
- Source
- Developmental Biology 480: 1-12 (Journal)
- Registered Authors
- Stainier, Didier
- Keywords
- Cardiac development, Cardiac wall morphogenesis, ErbB2 signaling, Hh signaling, Myocardium, Notch, Rbx1, Zebrafish
- MeSH Terms
-
- Animals
- Genes, erbB/genetics
- Myocytes, Cardiac/metabolism
- Myocardium/metabolism*
- Myocardial Contraction
- PubMed
- 34363825 Full text @ Dev. Biol.
Abstract
Cardiac trabeculae are muscular ridge-like structures within the ventricular wall that are crucial for cardiac function. In zebrafish, these structures first form primarily through the delamination of compact wall CMs. Although defects in proteasomal degradation have been associated with decreased cardiac function, whether they also affect cardiac development has not been extensively analyzed. Here we report a role during cardiac wall morphogenesis in zebrafish for the E3 ubiquitin-protein ligase Rbx1, which has been shown to regulate the degradation of key signaling molecules. Although development is largely unperturbed in zebrafish rbx1 mutant larvae, they exhibit cardiomyocyte multi-layering. This phenotype is not affected by blocking ErbB signaling, but fails to manifest itself in the absence of blood flow/cardiac contractility. Surprisingly, rbx1 mutants display ErbB independent Notch reporter expression in the myocardium. We generated tissue-specific rbx1 overexpression lines and found that endothelial, but not myocardial, specific rbx1 expression normalizes the cardiac wall morphogenesis phenotype. In addition, we found that pharmacological activation of Hedgehog signaling ameliorates the multi-layered myocardial wall phenotype in rbx1 mutants. Collectively, our data indicate that endocardial activity of Rbx1 is essential for cardiac wall morphogenesis.
Genes / Markers
Figure Gallery (6 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping