{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T21:59:29Z","timestamp":1785880769571,"version":"3.56.0"},"reference-count":63,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Congenital heart defects (CHDs) are common birth defects attributed to genetic and environmental factors, such as pharmaceuticals and chemicals. Identifying modifiable environmental factors and understanding their impact on heart development is crucial for mitigating chemical-induced CHDs. Given the increasing number of chemical agents, efficient high-throughput systems are essential to evaluate their teratogenic potential during cardiovascular development, which is a major concern for chemical safety. In this study, we developed 3 transgenic zebrafish reporter lines, myl7:EGFP, kdrl:mRFP, and gata1:mKate2, which enable real-time visualization of myocardial and endocardial development and cardiac function based on blood flow. These transgenic embryos were used to investigate the teratogenic effects of chemicals well known to induce heart defects in mammals, including humans. Our real-time imaging revealed that the teratogens induced significant malformations in cardiac morphogenesis, including abnormal heart tube formation, incomplete cardiac looping, and reduced heart chamber size. These teratogens also disrupted the expression of cardiac progenitor markers, suggesting impaired cardiac progenitor development. These defects were detected at the early stages (4\u201348\u2009h post-fertilization), suggesting that the stages of progenitor development to heart looping were most susceptible to teratogen exposure, i.e. the critical period for teratogen-induced heart defects. Functional defects, such as impaired blood flow, were observed using real-time imaging of the gata1-reporter line. This study demonstrates the utilization of transgenic zebrafish embryo models for high-throughput teratogenicity testing, which also allows us to analyze the mechanisms underlying chemical-induced heart defects. Therefore, our zebrafish models would contribute to the identification and reduction of risks associated with CHDs.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf083","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T07:36:11Z","timestamp":1749540971000},"page":"57-73","source":"Crossref","is-referenced-by-count":1,"title":["Chemical-induced heart defects using a transgenic zebrafish model"],"prefix":"10.1093","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6633-6806","authenticated-orcid":false,"given":"Shujie","family":"Liu","sequence":"first","affiliation":[{"name":"R&D, Safety Science Research, Kao Corporation , Kanagawa 210-0821,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kawanishi","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School of Science, University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuko","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Graduate School of Science, University of Tokyo , Tokyo 113-0033,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Nukada","sequence":"additional","affiliation":[{"name":"R&D, Safety Science Research, Kao Corporation , Tochigi 321-3497,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaaki","family":"Miyazawa","sequence":"additional","affiliation":[{"name":"R&D, Safety Science Research, Kao Corporation , Tochigi 321-3497,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7932-6358","authenticated-orcid":false,"given":"Hiroyuki","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Live Sciences, Kyoto Sangyo University , Kyoto 603-8555,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1798-5160","authenticated-orcid":false,"given":"Junichi","family":"Tasaki","sequence":"additional","affiliation":[{"name":"R&D, Safety Science Research, Kao Corporation , Kanagawa 210-0821,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"2025091914023239700_kfaf083-B1","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1517\/14740338.4.2.345","article-title":"Teratogenicity of sodium valproate","volume":"4","author":"Alsdorf","year":"2005","journal-title":"Expert Opin Drug Saf"},{"key":"2025091914023239700_kfaf083-B2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ajmg.1320290123","article-title":"Verification of the fetal valproate syndrome phenotype","volume":"29","author":"Ardinger","year":"1988","journal-title":"Am J Med Genet"},{"key":"2025091914023239700_kfaf083-B3","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1002\/bdrb.21168","article-title":"A developmental toxicology assay platform for screening teratogenic liability of pharmaceutical compounds","volume":"107","author":"Augustine-Rauch","year":"2016","journal-title":"Birth Defects Res. Part B Dev. Reprod Toxicol"},{"key":"2025091914023239700_kfaf083-B4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/cvr\/cvr098","article-title":"Zebrafish as a model to study cardiac development and human cardiac disease","volume":"91","author":"Bakkers","year":"2011","journal-title":"Cardiovasc Res"},{"key":"2025091914023239700_kfaf083-B5","doi-asserted-by":"crossref","first-page":"6121","DOI":"10.1242\/dev.00838","article-title":"Mutation of weak atrium\/atrial myosin heavy chain disrupts atrial function and influences ventricular morphogenesis in zebrafish","volume":"130","author":"Berdougo","year":"2003","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B6","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1111\/bph.15473","article-title":"Zebrafish as a tractable model of human cardiovascular disease","volume":"179","author":"Bowley","year":"2022","journal-title":"Br J Pharmacol"},{"key":"2025091914023239700_kfaf083-B7","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/bdrb.20223","article-title":"Development of a zebrafish embryo teratogenicity assay and quantitative prediction model","volume":"89","author":"Brannen","year":"2010","journal-title":"Birth Defects Res B Dev Reprod Toxicol"},{"key":"2025091914023239700_kfaf083-B8","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/S1534-5807(03)00363-0","article-title":"Isl1 identifies a cardiac progenitor population that proliferates prior to differentiation and contributes a majority of cells to the heart","volume":"5","author":"Cai","year":"2003","journal-title":"Dev Cell"},{"key":"2025091914023239700_kfaf083-B9","doi-asserted-by":"crossref","first-page":"135032","DOI":"10.1016\/j.jhazmat.2024.135032","article-title":"Oxidative damage and cardiotoxicity induced by 2-aminobenzothiazole in zebrafish (Danio rerio)","volume":"476","author":"Chen","year":"2024","journal-title":"J Hazard Mater"},{"key":"2025091914023239700_kfaf083-B10","doi-asserted-by":"crossref","first-page":"5341","DOI":"10.1093\/nar\/gkz218","article-title":"Deletion of Gtpbp3 in zebrafish revealed the hypertrophic cardiomyopathy manifested by aberrant mitochondrial tRNA metabolism","volume":"47","author":"Chen","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2025091914023239700_kfaf083-B11","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1242\/dev.123.1.293","article-title":"Mutations affecting the cardiovascular system and other internal organs in zebrafish","volume":"123","author":"Chen","year":"1996","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B12","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1242\/dev.122.12.3809","article-title":"Zebrafish tinman homolog demarcates the heart field and initiates myocardial differentiation","volume":"122","author":"Chen","year":"1996","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B13","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nrd4309","article-title":"Lessons learned from the fate of AstraZeneca\u2019s drug pipeline: a five-dimensional framework","volume":"13","author":"Cook","year":"2014","journal-title":"Nat Rev Drug Discov"},{"key":"2025091914023239700_kfaf083-B14","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1093\/eurheartj\/ehx032","article-title":"Anticoagulation for pregnant women with mechanical heart valves: a systematic review and meta-analysis","volume":"38","author":"D\u2019Souza","year":"2017","journal-title":"Eur. Heart J"},{"key":"2025091914023239700_kfaf083-B15","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/toxsci\/kfz165","article-title":"Comparison of zebrafish larvae and hiPSC cardiomyocytes for predicting drug-induced cardiotoxicity in humans","volume":"171","author":"Dyballa","year":"2019","journal-title":"Toxicol Sci"},{"key":"2025091914023239700_kfaf083-B16","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1161\/CIRCRESAHA.112.300853","article-title":"Genetics of congenital heart disease: the glass half empty","volume":"112","author":"Fahed","year":"2013","journal-title":"Circ Res"},{"key":"2025091914023239700_kfaf083-B17","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1038\/s41467-018-04402-6","article-title":"Continuous addition of progenitors forms the cardiac ventricle in zebrafish","volume":"9","author":"Felker","year":"2018","journal-title":"Nat Commun"},{"key":"2025091914023239700_kfaf083-B18","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/019131200750035058","article-title":"Microvascular perturbations in rats receiving the maximum tolerated dose of methotrexate or its major metabolite 7-hydroxymethotrexate","volume":"24","author":"Fuskevag","year":"2000","journal-title":"Ultrastruct Pathol"},{"key":"2025091914023239700_kfaf083-B19","doi-asserted-by":"crossref","first-page":"4635","DOI":"10.1242\/dev.129.19.4635","article-title":"The heartstrings mutation in zebrafish causes heart\/fin Tbx5 deficiency syndrome","volume":"129","author":"Garrity","year":"2002","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B20","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/bdrb.10007","article-title":"Comparison of developmental toxicology of aspirin (acetylsalicylic acid) in rats using selected dosing paradigms","volume":"68","author":"Gupta","year":"2003","journal-title":"Birth Defects Res B Dev Reprod Toxicol"},{"key":"2025091914023239700_kfaf083-B21","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1242\/dev.061473","article-title":"Zebrafish cardiac development requires a conserved secondary heart field","volume":"138","author":"Hami","year":"2011","journal-title":"Development"},{"issue":":","key":"2025091914023239700_kfaf083-B7728476","doi-asserted-by":"crossref","first-page":"e2404","DOI":"10.1002\/bdr2.2404","article-title":"Pharmacological inhibition of the spliceosome SF3b complex by pladienolide-B elicits craniofacial developmental defects in mouse and zebrafish","volume":"116","author":"Hoshino","year":"2024","journal-title":"Birth Defects Res"},{"key":"2025091914023239700_kfaf083-B22","doi-asserted-by":"crossref","first-page":"79","DOI":"10.2131\/fts.3.79","article-title":"Comparative study of the zebrafish embryonic toxicity test and mouse embryonic stem cell test to screen developmental toxicity of human pharmaceutical drugs","volume":"3","author":"Inoue","year":"2016","journal-title":"Fundam Toxicol Sci"},{"key":"2025091914023239700_kfaf083-B23","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/dbio.2000.9995","article-title":"The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development","volume":"230","author":"Isogai","year":"2001","journal-title":"Dev Biol"},{"key":"2025091914023239700_kfaf083-B24","doi-asserted-by":"crossref","first-page":"2995","DOI":"10.1161\/CIRCULATIONAHA.106.183216","article-title":"Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics","volume":"115","author":"Jenkins","year":"2007","journal-title":"Circulation"},{"key":"2025091914023239700_kfaf083-B25","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a037234","article-title":"Environmental risk factors for congenital heart disease","volume":"12","author":"Kalisch-Smith","year":"2020","journal-title":"Cold Spring Harb Perspect Biol."},{"key":"2025091914023239700_kfaf083-B26","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/bdra.20793","article-title":"Xenopus: an emerging model for studying congenital heart disease","volume":"91","author":"Kaltenbrun","year":"2011","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"key":"2025091914023239700_kfaf083-B27","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1126\/science.1101573","article-title":"Retinoic acid signaling restricts the cardiac progenitor pool","volume":"307","author":"Keegan","year":"2005","journal-title":"Science"},{"key":"2025091914023239700_kfaf083-B28","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1542\/peds.110.4.737","article-title":"Variables associated with medication errors in pediatric emergency medicine","volume":"110","author":"Kozer","year":"2002","journal-title":"Pediatrics"},{"key":"2025091914023239700_kfaf083-B29","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/pr.2014.128","article-title":"A detailed comparison of mouse and human cardiac development","volume":"76","author":"Krishnan","year":"2014","journal-title":"Pediatr Res"},{"key":"2025091914023239700_kfaf083-B30","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1056\/NEJM198510033131401","article-title":"Retinoic acid embryopathy","volume":"313","author":"Lammer","year":"1985","journal-title":"N Engl J Med"},{"key":"2025091914023239700_kfaf083-B31","doi-asserted-by":"crossref","first-page":"117165","DOI":"10.1016\/j.ecoenv.2024.117165","article-title":"Cardiovascular developmental hazards of valproic acid in zebrafish","volume":"286","author":"Lei","year":"2024","journal-title":"Ecotoxicol Environ Saf"},{"key":"2025091914023239700_kfaf083-B32","first-page":"257","author":"Liu","year":"2025"},{"key":"2025091914023239700_kfaf083-B33","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1093\/toxsci\/kfad078","article-title":"Identification of an adverse outcome pathway (AOP) for chemical-induced craniofacial anomalies using the transgenic zebrafish model","volume":"196","author":"Liu","year":"2023","journal-title":"Toxicol Sci"},{"issue":":","key":"2025091914023239700_kfaf083-B8655352","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1002\/dvdy.179","article-title":"Chemical-induced craniofacial anomalies caused by disruption of neural crest cell development in a zebrafish model","volume":"249","author":"Liu","year":"2020","journal-title":"Dev Dyn"},{"key":"2025091914023239700_kfaf083-B34","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/ije\/dyz009","article-title":"Global birth prevalence of congenital heart defects 1970-2017: updated systematic review and meta-analysis of 260 studies","volume":"48","author":"Liu","year":"2019","journal-title":"Int J Epidemiol"},{"key":"2025091914023239700_kfaf083-B35","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/1096-8628(200024)97:4<248::AID-AJMG1275>3.0.CO;2-C","article-title":"Vertebrate model systems in the study of early heart development: Xenopus and zebrafish","volume":"97","author":"Lohr","year":"2000","journal-title":"Am J Med Genet"},{"key":"2025091914023239700_kfaf083-B36","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1177\/8756479315598524","article-title":"Teratogens and congenital heart disease","volume":"31","author":"Lynch","year":"2015","journal-title":"J Diagnostic Med Sonogr"},{"key":"2025091914023239700_kfaf083-B37","doi-asserted-by":"crossref","first-page":"3139","DOI":"10.1242\/dev.02469","article-title":"Santa and valentine pattern concentric growth of cardiac myocardium in the zebrafish","volume":"133","author":"Mably","year":"2006","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B38","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1002\/bdrc.20219","article-title":"Cardiac developmental toxicity","volume":"93","author":"Mahler","year":"2011","journal-title":"Birth Defects Res C Embryo Today"},{"key":"2025091914023239700_kfaf083-B39","doi-asserted-by":"crossref","first-page":"592967","DOI":"10.3389\/fcell.2020.592967","article-title":"Chemical-induced cleft palate is caused and rescued by pharmacological modulation of the canonical Wnt signaling pathway in a zebrafish model","volume":"8","author":"Narumi","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"2025091914023239700_kfaf083-B40","volume-title":"The guide for the care and use of laboratory animals","author":"National Research Council. ed","year":"2011","edition":"8th ed"},{"key":"2025091914023239700_kfaf083-B41","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1161\/CIRCRESAHA.119.315378","article-title":"The FDA workshop on improving cardiotoxicity assessment with human-relevant platforms","volume":"125","author":"Pang","year":"2019","journal-title":"Circ Res"},{"key":"2025091914023239700_kfaf083-B42","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1592\/phco.2005.25.9.1271","article-title":"Acute cardiac toxicity associated with high-dose intravenous methotrexate therapy: case report and review of the literature","volume":"25","author":"Perez-Verdia","year":"2005","journal-title":"Pharmacotherapy"},{"key":"2025091914023239700_kfaf083-B43","doi-asserted-by":"crossref","first-page":"e653","DOI":"10.1161\/CIR.0000000000000606","article-title":"Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association","volume":"138","author":"Pierpont","year":"2018","journal-title":"Circulation"},{"key":"2025091914023239700_kfaf083-B44","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1242\/dev.127.2.225","article-title":"Induction and differentiation of the zebrafish heart requires fibroblast growth factor 8 (fgf8\/acerebellar)","volume":"127","author":"Reifers","year":"2000","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B45","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.reprotox.2011.08.003","article-title":"Feasibility study of the zebrafish assay as an alternative method to screen for developmental toxicity and embryotoxicity using a training set of 27 compounds","volume":"33","author":"Selderslaghs","year":"2012","journal-title":"Reprod Toxicol"},{"key":"2025091914023239700_kfaf083-B8755347","doi-asserted-by":"crossref","first-page":"721130","DOI":"10.3389\/fcell.2021.721130","article-title":"Validation, optimization, and application of the zebrafish developmental toxicity assay for pharmaceuticals under the ICH S5(R3) guideline","volume":"9","author":"Song","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2025091914023239700_kfaf083-B46","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1242\/dev.123.1.285","article-title":"Mutations affecting the formation and function of the cardiovascular system in the zebrafish embryo","volume":"123","author":"Stainier","year":"1996","journal-title":"Development"},{"key":"2025091914023239700_kfaf083-B47","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/35047564","article-title":"Zebrafish genetics and vertebrate heart formation","volume":"2","author":"Stainier","year":"2001","journal-title":"Nat Rev Genet"},{"key":"2025091914023239700_kfaf083-B48","doi-asserted-by":"crossref","DOI":"10.1136\/bcr-2012-007344","article-title":"Fetal warfarin syndrome","volume":"2012","author":"Starling","year":"2012","journal-title":"BMJ Case Rep"},{"key":"2025091914023239700_kfaf083-B5569297","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/978-1-60327-019-9_3","article-title":"Transgenesis in zebrafish with the Tol2 transposon system","volume":"561","author":"Suster","year":"2009","journal-title":"Methods Mol Biol"},{"key":"2025091914023239700_kfaf083-B49","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/tera.1420210210","article-title":"Retinoic acid-induced heart malformations in the hamster","volume":"21","author":"Taylor","year":"1980","journal-title":"Teratology"},{"key":"2025091914023239700_kfaf083-B50","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1093\/toxsci\/kfy250","article-title":"Automated morphological feature assessment for zebrafish embryo developmental toxicity screens","volume":"167","author":"Teixid\u00f3","year":"2019","journal-title":"Toxicol Sci"},{"key":"2025091914023239700_kfaf083-B51","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1126\/science.293.5535.1670","article-title":"UDP-glucose dehydrogenase required for cardiac valve formation in zebrafish","volume":"293","author":"Walsh","year":"2001","journal-title":"Science"},{"key":"2025091914023239700_kfaf083-B52","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.semcdb.2006.11.010","article-title":"Xenopus as a model system for vertebrate heart development","volume":"18","author":"Warkman","year":"2007","journal-title":"Semin Cell Dev Biol"},{"key":"2025091914023239700_kfaf083-B2345361","doi-asserted-by":"crossref","first-page":"108513","DOI":"10.1016\/j.reprotox.2023.108513","article-title":"Validation of a zebrafish developmental defects assay as a qualified alternative test for its regulatory use following the ICH S5(R3) guideline","volume":"123","author":"Weiner","year":"2024","journal-title":"Reprod Toxicol"},{"key":"2025091914023239700_kfaf083-B53","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1056\/NEJM198912143212404","article-title":"The relation of aspirin use during the first trimester of pregnancy to congenital cardiac defects","volume":"321","author":"Werler","year":"1989","journal-title":"N Engl J Med"},{"key":"2025091914023239700_kfaf083-B54","volume-title":"The zebrafish book: a guide for the laboratory use of zebrafish (Danio rerio)","author":"Westerfield","year":"2000","edition":"4th ed"},{"key":"2025091914023239700_kfaf083-B55","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1161\/01.CIR.97.18.1837","article-title":"Prediction of coronary heart disease using risk factor categories","volume":"97","author":"Wilson","year":"1998","journal-title":"Circulation"},{"key":"2025091914023239700_kfaf083-B56","author":"Wittig","year":"2020"},{"key":"2025091914023239700_kfaf083-B57","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.devcel.2012.06.005","article-title":"The LIM protein Ajuba restricts the second heart field progenitor pool by regulating Isl1 activity","volume":"23","author":"Witzel","year":"2012","journal-title":"Dev Cell"},{"key":"2025091914023239700_kfaf083-B58","doi-asserted-by":"crossref","first-page":"4689","DOI":"10.1093\/nar\/gkab228","article-title":"Ablation of Mto1 in zebrafish exhibited hypertrophic cardiomyopathy manifested by mitochondrion RNA maturation deficiency","volume":"49","author":"Zhang","year":"2021","journal-title":"Nucleic Acids Res"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfaf083\/63477898\/kfaf083.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/207\/1\/57\/63477898\/kfaf083.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/toxsci\/article-pdf\/207\/1\/57\/63477898\/kfaf083.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T18:02:49Z","timestamp":1758304969000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/207\/1\/57\/8160941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,12]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,6,12]]},"published-print":{"date-parts":[[2025,9,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfaf083","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,6,12]]}}}