title: Interaction of Wnt/β-catenin and notch signaling in the early stage of cardiac differentiation of P19CL6 cells.
abstract: Notch and Wnt/β-catenin signaling both play essential roles and interact closely in cardiomyocyte differentiation but the mechanism of interaction is largely unknown. Here we show that activation of Notch signaling in undifferentiated P19CL6 cells promoted cardiac differentiation, indicated by upregulated expression of early cardiac markers and activated the canonical Wnt pathway, suggested by augmented nuclear translocation of β-catenin. Further activation of the Notch pathway in early differentiating cells (at day 3) inhibited expression of a specific cardiac progenitor marker Islet1 but had no influence on β-catenin translocation. Notch signaling thus played biphasic roles in the early stage of cardiomyocyte differentiation and Wnt/β-catenin signaling. Unlike Notch signaling, Wnt signaling promoted cardiomyocyte differentiation and activated the Notch pathway in either undifferentiated or early differentiating cells. Additionally, β-catenin, recombination signal sequence binding protein-Jkappa (RBP-Jκ), and Notch1 intracellular domain (NICD-1) formed a transcriptional complex which was recruited to the Hes1 promoter region, indicating direct transcriptional regulation of Hes1. We thus document a specific reciprocal interaction between these two signaling pathways during early stage cardiac differentiation of P19CL6 cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education of China, Peking University, Beijing 100191, China.
authors.forename: Binhong
authors.initials: B
authors.lastname: Li
authors.forename: Zhuqing
authors.initials: Z
authors.lastname: Jia
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Weiping
authors.initials: W
authors.lastname: Wang
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zhang
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Kangtao
authors.initials: K
authors.lastname: Ma
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology; D018021:Lithium Chloride / Q000494:pharmacology; D049410:Luciferases, Renilla / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D020239:Receptor Cross-Talk; D051881:Receptor, Notch1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000072056:Transcription Factor HES-1; D014158:Transcription, Genetic; D060449:Wnt Signaling Pathway; D060509:Wnt3A Protein / Q000494:pharmacology / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D051819:Immunoglobulin J Recombination Signal Sequence-Binding Protein; D036341:Intercellular Signaling Peptides and Proteins; D018021:Lithium Chloride; D049410:Luciferases, Renilla; D046912:Multiprotein Complexes; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; D060509:Wnt3A Protein; D051176:beta Catenin; C501127:Dkk1 protein, mouse; C489734:Hes1 protein, mouse; C497762:Notch1 protein, mouse; C497571:Rbpj protein, mouse; C555511:Wnt3a protein, mouse