title: A novel role of CDX1 in embryonic epicardial development.
abstract: The molecular mechanism that regulates epicardial development has yet to be understood. In this study, we explored the function of CDX1, a Caudal-related family member, in epicardial epithelial-to-mesenchymal transition (EMT) and in the migration and the differentiation of epicardium-derived progenitors into vascular smooth muscle cells. We detected a transient expression of CDX1 in murine embryonic hearts at 11.5 days post coitum (dpc). Using a doxycycline-inducible CDX1 mouse model, primary epicardium, and ex vivo heart culture, we further demonstrated that ectopic expression of CDX1 promoted epicardial EMT. In addition, a low-dose CDX1 induction led to enhanced migration and differentiation of epicardium-derived cells into α-SMA+ vascular smooth muscles. In contrast, either continued high-level induction of CDX1 or CDX1 deficiency attenuated the ability of epicardium-derived cells to migrate and to mature into smooth muscles induced by TGF-β1. Further RNA-seq analyses showed that CDX1 induction altered the transcript levels of genes involved in neuronal development, angiogenesis, and cell adhesions required for EMT. Our data have revealed a previously undefined role of CDX1 during epicardial development, and suggest that transient expression of CDX1 promotes epicardial EMT, whereas subsequent down-regulation of CDX1 after 11.5 dpc in mice is necessary for further subepicardial invasion of EPDCs and contribution to coronary vascular endothelium or smooth muscle cells.
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Min
authors: M
authors: Chu
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Libo
authors: L
authors: Wang
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Huan
authors: H
authors: Wang
authors: State Key Laboratory of Genetics Engineering & MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors: Ting
authors: T
authors: Shen
authors: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors: Yanqin
authors: Y
authors: Yang
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Yun
authors: Y
authors: Sun
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Nannan
authors: N
authors: Tang
authors: State Key Laboratory of Genetics Engineering & MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.
authors: Ting
authors: T
authors: Ni
authors: Systems Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors: Jun
authors: J
authors: Zhu
authors: Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, United States of America.
authors: Richard B
authors: RB
authors: Mailman
authors: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors: Yuan
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003330:Coronary Vessel Anomalies / Q000235:genetics; D053595:Embryonic Stem Cells; D004730:Endothelium, Vascular / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis / Q000235:genetics; D038081:Organogenesis / Q000235:genetics*; D010496:Pericardium / Q000196:embryology* / Q000378:metabolism*; D010641:Phenotype
chemical_list: C491272:Cdx1 protein, mouse; D018398:Homeodomain Proteins