scotch tape Encodes a Novel Transmembrane Protein Essential for Cardiac Valve Development in Zebrafish
会议名称：《中国的遗传学研究——遗传学进步推动中国西部经济与社会发...》
会议日期：2011年
学科分类：0710[理学-生物学] 071010[理学-生物化学与分子生物学] 07[理学]
基 金：the National Basic Research Program of China(2007CB12100 and 2010CB529503) National Science Foundation of China(30971662)
关 键 词：scotch tape heart valve endocardium zebrafish
摘 要：Defects in cardiac valve morphogenesis are common causes of human congenital heart diseases,however the underlying cellular and molecular components remain largely unknown. The zebrafish scotch tape(sco) mutant showed severe cardiac edema,affected atrioventricular (AV) canal restriction and caused an abnormal caudal fin.Cardiac jelly,located between the endocardial and myocardial basement membranes,was almost undetectable by laminin staining, while chondroitin sulfate,a modified proteoglycan in the cardiac jelly,was present in sco mutants. High-speed movies showed no apparent endocardial invagination in the AV canal in the sco mutant heart at 72 hpf,leading to retrograde flow of blood from ventricle to atrium.The heart valve defects were due to abnormal expression of several valve markers,including bmp4. br146/versican,tbx2b,and notch 1b.Positional cloning revealed that sco encodes a novel 540 amino acid protein with one putative transmembrane domain and three IgG domains. Overexpression of sco in the endocardium and endothelial cells,but not in the myocardium,could rescue sco mutant phenotype,supporting its primary role in the endocardium.Notch signaling was not activated in the AV canal of sco mutant hearts while it was otherwise active during normal endocardial cushion development.Abnormal expression of cell adhesion gene VE-cadherin,tight junction protein ZO1 and cell polarity protein aPKC compromised endocardial invagination of epithelial-mesenchymal transition(EMT) in the AV canal of sco mutants.Therefore,sco is an important factor for regulating endocardial and cardiac valve morphogenesis.