title: Vinculin b deficiency causes epicardial hyperplasia and coronary vessel disorganization in zebrafish.
abstract: Coronary vessel development is a highly coordinated process during heart formation. Abnormal development and dysfunction of the coronary network are contributory factors in the majority of heart disease. Understanding the molecular mechanisms that regulate coronary vessel formation is crucial for preventing and treating the disease. We report a zebrafish gene-trap vinculin b (vclb) mutant that displays abnormal coronary vessel development among multiple cardiac defects. The mutant shows overproliferation of epicardium-derived cells and disorganization of coronary vessels, and they eventually die off at juvenile stages. Mechanistically, Vclb deficiency results in the release of another cytoskeletal protein, paxillin, from the Vclb complex and the upregulation of ERK and FAK phosphorylation in epicardium and endocardium, causing disorganization of endothelial cells and pericytes during coronary vessel development. By contrast, cardiac muscle development is relatively normal, probably owing to redundancy with Vcla, a vinculin paralog that is expressed in the myocardium but not epicardium. Together, our results reveal a previously unappreciated function of vinculin in epicardium and endocardium and reinforce the notion that well-balanced FAK activity is essential for coronary vessel development.
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Feng
authors: F
authors: Cheng
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors: Liyun
authors: L
authors: Miao
authors: Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100871, China.
authors: Qing
authors: Q
authors: Wu
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors: Xia
authors: X
authors: Gong
authors: Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100871, China jingwei_xiong@pku.edu.cn jianzhang84@genetics.ac.cn.
authors: Jingwei
authors: J
authors: Xiong
authors: State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China jingwei_xiong@pku.edu.cn jianzhang84@genetics.ac.cn.
authors: Jian
authors: 0000-0002-5867-9808
authors: J
authors: Zhang
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000196:embryology / Q000378:metabolism* / Q000473:pathology*; D004699:Endocardium / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006321:Heart / Q000196:embryology; D006965:Hyperplasia / Q000378:metabolism* / Q000473:pathology; D010496:Pericardium / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D016596:Vinculin / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; D016596:Vinculin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Coronary vessel; Cytoskeleton; Epicardium; Vinculin; Zebrafish