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

Sarvari, P., Rasouli, S. J., Allanki, S., Stone, O. A., Sokol, A. M., Graumann, J., et al. (2021). The E3 ubiquitin-protein ligase Rbx1 regulates cardiac wall morphogenesis in zebrafish. DEVELOPMENTAL BIOLOGY, 480, 1-12. doi:10.1016/j.ydbio.2021.07.019.

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 Creators:
Sarvari, Pourya1, Author              
Rasouli, S. Javad1, Author              
Allanki, Srinivas1, Author              
Stone, Oliver A.1, Author              
Sokol, Anna M.2, Author              
Graumann, Johannes2, Author              
Stainier, Didier Y. R.1, Author              
Affiliations:
1Developmental Genetics, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591697              
2Biomolecular Mass Spectrometry, Max Planck Institute for Heart and Lung Research, Max Planck Society, ou_2591705              

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Free keywords: OUTFLOW TRACT; CELL-CYCLE; HEART; REVEALS; HEDGEHOG; ERBB2; IDENTIFICATION; PROLIFERATION; DISRUPTION; ACTIVATIONDevelopmental Biology; Cardiac development; Cardiac wall morphogenesis; Myocardium; Zebrafish; Rbx1; Notch; ErbB2 signaling; Hh signaling;
 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 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.

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Language(s): eng - English
 Dates: 2021-08-042021-12
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: DEVELOPMENTAL BIOLOGY
Source Genre: Journal
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Publ. Info: 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA : ACADEMIC PRESS INC ELSEVIER SCIENCE
Pages: - Volume / Issue: 480 Sequence Number: - Start / End Page: 1 - 12 Identifier: ISSN: 0012-1606