{"doi":"10.1242/jcs.03186","title":"Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis","abstract":"<jats:p>Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate transcription. Drosophila Mef2 is essential for Drosophila heart development, however, neither MEF2C nor MEF2B are essential for the early stages of murine cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of heart morphogenesis, differentiation of cardiomyocytes still occurred. Since there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the ability of cells to differentiate may have been confounded by genetic redundancy. To eliminate this variable, the effect of a dominant-negative MEF2 mutant (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19 cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5 enhancer in the P19 system resulted in the loss of both cardiomyocyte development and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and exhibited defective differentiation. Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals.</jats:p>","journal":"Journal of Cell Science","year":2006,"id":653740,"datarank":2.3358492634310664,"base_score":4.174387269895637,"endowment":4.174387269895637,"self_citation_contribution":0.6261580904843456,"citation_network_contribution":1.7096911729467208,"self_endowment_contribution":0.6261580904843456,"citer_contribution":1.7096911729467208,"corpus_percentile":null,"corpus_rank":null,"citation_count":64,"citer_count":56,"citers_with_citation_signal":44,"citers_with_endowment":44,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1705791,"name":"Gabriel D. Dakubo","orcid":null,"position":1,"is_corresponding":false},{"id":783560,"name":"Jun Liu","orcid":"0000-0002-8175-6293","position":2,"is_corresponding":false},{"id":566964,"name":"Yves De Repentigny","orcid":"0000-0001-8408-2442","position":3,"is_corresponding":false},{"id":1705792,"name":"Katherine Yutzey","orcid":null,"position":4,"is_corresponding":false},{"id":825829,"name":"Valerie A. Wallace","orcid":"0000-0003-3721-9017","position":5,"is_corresponding":false},{"id":566967,"name":"Rashmi Kothary","orcid":"0000-0002-9239-7310","position":6,"is_corresponding":false},{"id":1705793,"name":"Ilona S. Skerjanc","orcid":null,"position":7,"is_corresponding":false},{"id":898982,"name":"Christina Karamboulas","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Disruption of MEF2 activity in cardiomyoblasts inhibits cardiomyogenesis","abstract":"<jats:p>Myocyte enhancer factors (MEF2s) bind to muscle-specific promoters and activate transcription. Drosophila Mef2 is essential for Drosophila heart development, however, neither MEF2C nor MEF2B are essential for the early stages of murine cardiomyogenesis. Although Mef2c-null mice were defective in the later stages of heart morphogenesis, differentiation of cardiomyocytes still occurred. Since there are four isoforms of MEF2 factors (MEF2A, MEF2B, MEF2C and MEF2D), the ability of cells to differentiate may have been confounded by genetic redundancy. To eliminate this variable, the effect of a dominant-negative MEF2 mutant (MEF2C/EnR) during cardiomyogenesis was examined in transgenic mice and P19 cells. Targeting the expression of MEF2C/EnR to cardiomyoblasts using an Nkx2-5 enhancer in the P19 system resulted in the loss of both cardiomyocyte development and the expression of GATA4, BMP4, Nkx2-5 and MEF2C. In transiently transgenic mice, MEF2C/EnR expression resulted in embryos that lacked heart structures and exhibited defective differentiation. Our results show that MEF2C, or genes containing MEF2 DNA-binding sites, is required for the efficient differentiation of cardiomyoblasts into cardiomyocytes, suggesting conservation in the role of MEF2 from Drosophila to mammals.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17003108","pmcid":null,"openalex_id":null,"authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":null,"license":null,"oa_locations":[{"url":"http://journals.biologists.com/jcs/article-pdf/119/20/4315/1368817/4315.pdf","host_type":"publisher"}],"fields_of_study":[],"mesh_terms":["Myocardium","Cell Line, Tumor","Animals","Mice, Inbred C3H","Mice, Inbred C57BL","Mice, Transgenic","Mice","Myogenic Regulatory Factors","Homeodomain Proteins","Transcription Factors","Blotting, Northern","In Situ Hybridization","Reverse Transcriptase Polymerase Chain Reaction","Cell Differentiation","Cell Aggregation","Binding Sites","Protein Binding","Muscle Development","Models, Biological","Female","Male","GATA4 Transcription Factor","MEF2 Transcription Factors","Homeobox Protein Nkx-2.5"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-11T00:19:42.489433Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}