Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8467117 | Developmental Biology | 2018 | 24 Pages |
Abstract
Coronary artery anomalies are common congenital disorders with serious consequences in adult life. Coronary circulation begins when the coronary stems form connections between the aorta and the developing vascular plexus. We recently identified the WNT signaling modulator R-spondin 3 (Rspo3), as a crucial regulator of coronary stem proliferation. Using expression analysis and tissue-specific deletion we now demonstrate that Rspo3 is primarily produced by cardiomyocytes. Moreover, we have employed CRISPR/Cas9 technology to generate novel Lgr4-null alleles that showed a significant decrease in coronary stem proliferation and thus phenocopied the coronary artery defects seen in Rspo3 mutants. Interestingly, Lgr4 mutants displayed slightly hypomorphic right ventricles, an observation also made after myocardial specific deletion of Rspo3. These results shed new light on the role of Rspo3 in heart development and demonstrate that LGR4 is the principal R-spondin 3 receptor in the heart.
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Authors
Fabio Da Silva, Filippo Massa, Fariba Jian Motamedi, Valerie Vidal, Ana Sofia Rocha, Elodie P. Gregoire, Chen-Leng Cai, Kay Dietrich Wagner, Andreas Schedl,