The E3 ubiquitin-protein ligase Rbx1 regulates cardiac wall morphogenesis in zebrafish.

Autor: Sarvari P; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany., Rasouli SJ; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany., Allanki S; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany., Stone OA; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany., Sokol AM; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany; Max Planck Institute for Heart and Lung Research, Biomolecular Mass Spectrometry, Bad Nauheim, 61231, Germany., Graumann J; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany; Max Planck Institute for Heart and Lung Research, Biomolecular Mass Spectrometry, Bad Nauheim, 61231, Germany., Stainier DYR; Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, Bad Nauheim, 61231, Germany. Electronic address: Didier.Stainier@mpi-bn.mpg.de.
Jazyk: angličtina
Zdroj: Developmental biology [Dev Biol] 2021 Dec; Vol. 480, pp. 1-12. Date of Electronic Publication: 2021 Aug 04.
DOI: 10.1016/j.ydbio.2021.07.019
Abstrakt: 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 cardiomyocytes (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 CM 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.
Competing Interests: Declaration of competing interest All the authors declare no competing of interest.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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