{"doi":"10.1073/pnas.0400752101","title":"GATA4 is essential for formation of the proepicardium and regulates cardiogenesis","abstract":"<jats:p>\n                    The role of GATA4 during the earliest stages of cardiogenesis has not been defined because\n                    <jats:italic>Gata4</jats:italic>\n                    knockout embryos suffer an early developmental arrest caused by deficiencies in extraembryonic visceral endoderm function. We have used tetraploid embryo complementation to rescue these defects and generated clonal embryonic day 9.5\n                    <jats:italic>Gata4</jats:italic>\n                    <jats:sup>–/–</jats:sup>\n                    embryos directly from embryonic stem cells. GATA4-null embryos display heart defects characterized by disrupted looping morphogenesis, septation, and a hypoplastic ventricular myocardium. We find that myocardial gene expression is relatively normal in GATA4-null hearts including expression of GATA6. Moreover, GATA4 expression in the endocardium is dispensable for trabeculae formation. Remarkably, the proepicardium is absent in GATA4-null embryos, blocking formation of the epicardium. Therefore, we propose that the observed myocardial defects may be a secondary consequence of loss of the proepicardium. These findings definitively demonstrate a requirement for GATA4 during early cardiac development and identify an essential factor for generation of the proepicardium.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2004,"id":632293,"datarank":0.881660367266946,"base_score":5.877735781779639,"endowment":5.877735781779639,"self_citation_contribution":0.881660367266946,"citation_network_contribution":0.0,"self_endowment_contribution":0.881660367266946,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":356,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":454148,"name":"Michele A. Battle","orcid":null,"position":1,"is_corresponding":false},{"id":918365,"name":"Jixuan Li","orcid":"0000-0001-8084-0314","position":2,"is_corresponding":false},{"id":545757,"name":"Stephen A. Duncan","orcid":"0000-0002-2507-7827","position":3,"is_corresponding":false},{"id":1638906,"name":"Alistair J. Watt","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"GATA4 is essential for formation of the proepicardium and regulates cardiogenesis","abstract":"<jats:p>\n                    The role of GATA4 during the earliest stages of cardiogenesis has not been defined because\n                    <jats:italic>Gata4</jats:italic>\n                    knockout embryos suffer an early developmental arrest caused by deficiencies in extraembryonic visceral endoderm function. We have used tetraploid embryo complementation to rescue these defects and generated clonal embryonic day 9.5\n                    <jats:italic>Gata4</jats:italic>\n                    <jats:sup>–/–</jats:sup>\n                    embryos directly from embryonic stem cells. GATA4-null embryos display heart defects characterized by disrupted looping morphogenesis, septation, and a hypoplastic ventricular myocardium. We find that myocardial gene expression is relatively normal in GATA4-null hearts including expression of GATA6. Moreover, GATA4 expression in the endocardium is dispensable for trabeculae formation. Remarkably, the proepicardium is absent in GATA4-null embryos, blocking formation of the epicardium. Therefore, we propose that the observed myocardial defects may be a secondary consequence of loss of the proepicardium. These findings definitively demonstrate a requirement for GATA4 during early cardiac development and identify an essential factor for generation of the proepicardium.\n                  </jats:p>","is_dataset_classified":null,"base_score":5.877735781779639,"endowment":5.877735781779639,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"15310850","pmcid":"PMC515098","openalex_id":"https://openalex.org/W2019127826","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK060064","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"F32 DK067808","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK055743","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK 60064","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK 55743","title":null}],"total_grants":5,"fwci":6.9255,"citation_percentile":0.97948408,"influential_citations":0,"citation_trend":[{"year":2012,"count":23},{"year":2013,"count":20},{"year":2014,"count":22},{"year":2015,"count":16},{"year":2016,"count":13},{"year":2017,"count":18},{"year":2018,"count":17},{"year":2019,"count":11},{"year":2020,"count":10},{"year":2021,"count":16},{"year":2022,"count":16},{"year":2023,"count":10},{"year":2024,"count":16},{"year":2025,"count":8},{"year":2026,"count":5}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/515098","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/515098","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.0400752101","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.0400752101","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/15310850","host_type":"repository"}],"fields_of_study":["Congenital heart defects research","RNA modifications and cancer","Congenital Heart Disease Studies"],"mesh_terms":["Animals","DNA-Binding Proteins","Embryo, Mammalian","Embryonic Structures","Genetic Complementation Test","Heart","Heart Defects, Congenital","Morphogenesis","Myocardium","Pericardium","Stem Cells","Transcription Factors","Mice, Knockout","GATA4 Transcription Factor","Mice"],"keywords":["GATA4","Embryonic stem cell","Heart development","Biology","Endoderm","Cell biology","Embryo","Morphogenesis","Embryogenesis","Endocardium","Internal medicine","Genetics","Gene expression","Gene","Medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T09:28:03.744370Z","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":[]}