{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:55:34Z","timestamp":1789707334741,"version":"4.0.1"},"reference-count":107,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T00:00:00Z","timestamp":1681257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>The <jats:italic>Drosophila<\/jats:italic> heart tube seems simple, yet it has notable anatomic complexity and contains highly specialized structures. In fact, the development of the fly heart tube much resembles that of the earliest stages of mammalian heart development, and the molecular-genetic mechanisms driving these processes are highly conserved between flies and humans. Combined with the fly\u2019s unmatched genetic tools and a wide variety of techniques to assay both structure and function in the living fly heart, these attributes have made <jats:italic>Drosophila<\/jats:italic> a valuable model system for studying human heart development and disease. This perspective focuses on the functional and physiological similarities between fly and human hearts. Further, it discusses current limitations in using the fly, as well as promising prospects to expand the capabilities of <jats:italic>Drosophila<\/jats:italic> as a research model for studying human cardiac diseases.<\/jats:p>","DOI":"10.3389\/fphys.2023.1182610","type":"journal-article","created":{"date-parts":[[2023,4,12]],"date-time":"2023-04-12T05:54:55Z","timestamp":1681278895000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["The opportunities and challenges of using Drosophila to model human cardiac diseases"],"prefix":"10.3389","volume":"14","author":[{"given":"Yunpo","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce","family":"van de Leemput","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1002\/dvdy.24530","article-title":"Conserved signaling mechanisms in Drosophila heart development","volume":"246","author":"Ahmad","year":"2017","journal-title":"Dev. Dyn."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2499","DOI":"10.1093\/hmg\/11.20.2499","article-title":"Phenotypic diversity in hypertrophic cardiomyopathy","volume":"11","author":"Arad","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"B3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.2337\/dc16-1889","article-title":"Association of cardiovascular risk factors and myocardial fibrosis with early cardiac dysfunction in type 1 diabetes: The diabetes control and complications trial\/epidemiology of diabetes interventions and complications study","volume":"40","author":"Armstrong","year":"2017","journal-title":"Diabetes Care"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1647","DOI":"10.1016\/j.cell.2019.11.025","article-title":"A spatiotemporal organ-wide gene expression and cell atlas of the developing human heart","volume":"179","author":"Asp","year":"2019","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e51114","DOI":"10.7554\/eLife.51114","article-title":"Straightjacket\/\u03b12\u03b43 deregulation is associated with cardiac conduction defects in myotonic dystrophy type 1","volume":"8","author":"Auxerre-Planti\u00e9","year":"2019","journal-title":"Elife"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1101\/gad.7.7b.1325","article-title":"Tinman and bagpipe: two homeo box genes that determine cell fates in the dorsal mesoderm of Drosophila","volume":"7","author":"Azpiazu","year":"1993","journal-title":"Genes Dev."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e95085","DOI":"10.1172\/jci.insight.95085","article-title":"Epigenetic mechanisms underlying maternal diabetes-associated risk of congenital heart disease","volume":"2","author":"Basu","year":"2017","journal-title":"JCI Insight"},{"key":"B8","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1203\/PDR.0b013e318191fc68","article-title":"The epicurean fly: Using Drosophila melanogaster to study metabolism","volume":"65","author":"Bharucha","year":"2009","journal-title":"Pediatr. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1016\/j.cmet.2010.09.014","article-title":"High-fat-diet-induced obesity and heart dysfunction are regulated by the TOR pathway in Drosophila","volume":"12","author":"Birse","year":"2010","journal-title":"Cell Metab."},{"key":"B10","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/1050-1738(94)00032-Q","article-title":"Heart development in Drosophila and its relationship to vertebrates","volume":"5","author":"Bodmer","year":"1995","journal-title":"Trends cardiovasc. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1242\/dev.118.3.719","article-title":"The gene tinman is required for specification of the heart and visceral muscles in Drosophila","volume":"118","author":"Bodmer","year":"1993","journal-title":"Development"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e31515","DOI":"10.7554\/eLife.31515","article-title":"Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt\/\u03b2-catenin signaling in autonomic control of heart rate","volume":"7","author":"Burkhard","year":"2018","journal-title":"Elife"},{"key":"B13","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1111\/acel.12559","article-title":"Expression patterns of cardiac aging in Drosophila","volume":"16","author":"Cannon","year":"2017","journal-title":"Aging Cell"},{"key":"B14","doi-asserted-by":"publisher","first-page":"a034173","DOI":"10.1101\/cshperspect.a034173","article-title":"Vagus nerve stimulation and the cardiovascular system","volume":"10","author":"Capilupi","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.ydbio.2016.03.008","article-title":"Wnt4 is required for ostia development in the Drosophila heart","volume":"413","author":"Chen","year":"2016","journal-title":"Dev. Biol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"802393","DOI":"10.3389\/fgene.2022.802393","article-title":"GOing forward with the cardiac conduction system using gene ontology","volume":"13","author":"Chloe Li","year":"2022","journal-title":"Front. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"dev171983","DOI":"10.1242\/dev.171983","article-title":"Genetic and epigenetic regulation of cardiomyocytes in development, regeneration and disease","volume":"145","author":"Cui","year":"2018","journal-title":"Development"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1934","DOI":"10.1016\/j.celrep.2019.01.079","article-title":"Single-cell transcriptome analysis maps the developmental track of the human heart","volume":"26","author":"Cui","year":"2019","journal-title":"Cell Rep."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1089\/ars.2011.4179","article-title":"Cardiac aging: From molecular mechanisms to significance in human health and disease","volume":"16","author":"Dai","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"B20","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/j.devcel.2016.10.001","article-title":"Single-cell resolution of temporal gene expression during heart development","volume":"39","author":"DeLaughter","year":"2016","journal-title":"Dev. Cell"},{"key":"B21","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/ng.2610","article-title":"Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders","volume":"45","author":"den Hoed","year":"2013","journal-title":"Nat. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1523\/JNEUROSCI.2906-04.2005","article-title":"Glutamatergic innervation of the heart initiates retrograde contractions in adult Drosophila melanogaster","volume":"25","author":"Dulcis","year":"2005","journal-title":"J. Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e003108","DOI":"10.1161\/CIRCGEN.120.003108","article-title":"Exome sequencing and congenital heart disease in sub-saharan africa","volume":"14","author":"Ekure","year":"2021","journal-title":"Circ. Genom Precis. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/biomedicines11020524","article-title":"Hypertrophic, dilated, and arrhythmogenic cardiomyopathy: Where are we?","volume":"11","author":"El Hadi","year":"2023","journal-title":"Biomedicines"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e43882","DOI":"10.7554\/eLife.43882","article-title":"Single-cell expression profiling reveals dynamic flux of cardiac stromal, vascular and immune cells in health and injury","volume":"8","author":"Farbehi","year":"2019","journal-title":"Elife"},{"key":"B26","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1161\/CIRCRESAHA.110.221531","article-title":"The multiple phases and faces of wnt signaling during cardiac differentiation and development","volume":"107","author":"Gessert","year":"2010","journal-title":"Circ. Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1161\/CIRCULATIONAHA.117.030742","article-title":"Single-cell sequencing of the healthy and diseased heart reveals cytoskeleton-associated protein 4 as a new modulator of fibroblasts activation","volume":"138","author":"Gladka","year":"2018","journal-title":"Circulation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"e75","DOI":"10.1161\/STROKEAHA.121.038273","article-title":"Research opportunities in stroke prevention for atrial fibrillation: A report from a national heart, lung, and blood institute virtual workshop","volume":"54","author":"Go","year":"2023","journal-title":"Stroke"},{"key":"B29","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1161\/CIRCRESAHA.118.314578","article-title":"Transcriptomic profiling of the developing cardiac conduction system at single-cell resolution","volume":"125","author":"Goodyer","year":"2019","journal-title":"Circ. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1038\/s41569-018-0061-5","article-title":"Cardiac ageing: Extrinsic and intrinsic factors in cellular renewal and senescence","volume":"15","author":"Gude","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/s41467-018-08128-3","article-title":"Intergenerational inheritance of high fat diet-induced cardiac lipotoxicity in Drosophila","volume":"10","author":"Guida","year":"2019","journal-title":"Nat. Commun."},{"key":"B32","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ajhg.2013.06.006","article-title":"ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy","volume":"93","author":"Haack","year":"2013","journal-title":"Am. J. Hum. Genet."},{"key":"B33","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1534\/genetics.115.183392","article-title":"Genetics on the fly: A primer on the Drosophila model system","volume":"201","author":"Hales","year":"2015","journal-title":"Genetics"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1161\/CIRCRESAHA.120.318458","article-title":"Innervation and neuronal control of the mammalian sinoatrial node a comprehensive atlas","volume":"128","author":"Hanna","year":"2021","journal-title":"Circ. Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1017\/S1047951116002079","article-title":"Cardiac manifestations of congenital LMNA-related muscular dystrophy in children: Three case reports and recommendations for care","volume":"27","author":"Heller","year":"2017","journal-title":"Cardiol. Young"},{"key":"B36","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1146\/annurev-ento-011019-025003","article-title":"The insect circulatory system: Structure, function, and evolution","volume":"65","author":"Hillyer","year":"2020","journal-title":"Annu. Rev. Entomol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1126\/science.aac9396","article-title":"De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies","volume":"350","author":"Homsy","year":"2015","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e50163","DOI":"10.7554\/eLife.50163","article-title":"Single-cell analysis uncovers that metabolic reprogramming by ErbB2 signaling is essential for cardiomyocyte proliferation in the regenerating heart","volume":"8","author":"Honkoop","year":"2019","journal-title":"Elife"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1101\/gad.316802.118","article-title":"Single-nucleus transcriptomic survey of cell diversity and functional maturation in postnatal mammalian hearts","volume":"32","author":"Hu","year":"2018","journal-title":"Genes Dev."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1016\/j.ajhg.2018.03.022","article-title":"Mutations in PPCS, encoding phosphopantothenoylcysteine synthetase, cause autosomal-recessive dilated cardiomyopathy","volume":"102","author":"Iuso","year":"2018","journal-title":"Am. J. Hum. Genet."},{"key":"B41","doi-asserted-by":"publisher","first-page":"4877","DOI":"10.1038\/s41467-018-07307-6","article-title":"Single cell RNA-seq and ATAC-seq analysis of cardiac progenitor cell transition states and lineage settlement","volume":"9","author":"Jia","year":"2018","journal-title":"Nat. Commun."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1038\/ng.3970","article-title":"Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands","volume":"49","author":"Jin","year":"2017","journal-title":"Nat. Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1002\/1097-010x(20010201)289:2<81::aid-jez1>3.0.co;2-t","article-title":"Dynamin, encoded by shibire, is central to cardiac function","volume":"289","author":"Johnson","year":"2001","journal-title":"J. Exp. Zool."},{"key":"B44","doi-asserted-by":"publisher","first-page":"jeb242699","DOI":"10.1242\/jeb.242699","article-title":"Myogenic contraction of a somatic muscle powers rhythmic flow of hemolymph through Drosophila antennae and generates brain pulsations","volume":"224","author":"Kay","year":"2021","journal-title":"J. Exp. Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1030950","DOI":"10.3389\/fcell.2022.1030950","article-title":"Genome organization in cardiomyocytes expressing mutated A-type lamins","volume":"10","author":"Kervella","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1607","DOI":"10.1242\/jeb.004887","article-title":"Common aging pathways in worms, flies, mice and humans","volume":"210","author":"Kim","year":"2007","journal-title":"J. Exp. Biol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e20851","DOI":"10.7554\/eLife.20851","article-title":"Age-dependent diastolic heart failure in an in vivo Drosophila model","volume":"6","author":"Klassen","year":"2017","journal-title":"Elife"},{"key":"B48","doi-asserted-by":"publisher","first-page":"8145","DOI":"10.1073\/pnas.90.17.8145","article-title":"Csx: A murine homeobox-containing gene specifically expressed in the developing heart","volume":"90","author":"Komuro","year":"1993","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B49","doi-asserted-by":"publisher","first-page":"e38064","DOI":"10.7554\/eLife.38064","article-title":"Prolonged cross-bridge binding triggers muscle dysfunction in a Drosophila model of myosin-based hypertrophic cardiomyopathy","volume":"7","author":"Kronert","year":"2018","journal-title":"Elife"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1502","DOI":"10.1016\/j.cub.2006.05.064","article-title":"Control of cardiac rhythm by ORK1, a Drosophila two-pore domain potassium channel","volume":"16","author":"Lalev\u00e9e","year":"2006","journal-title":"Curr. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1161\/circresaha.116.309386","article-title":"Pediatric cardiomyopathies","volume":"121","author":"Lee","year":"2017","journal-title":"Circ. Res."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1126\/science.aao4174","article-title":"Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq","volume":"359","author":"Lescroart","year":"2018","journal-title":"Science"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1007\/s11886-022-01756-8","article-title":"Wnt signaling in heart development and regeneration","volume":"24","author":"Li","year":"","journal-title":"Curr. Cardiol. Rep."},{"key":"B54","doi-asserted-by":"publisher","first-page":"dev173476","DOI":"10.1242\/dev.173476","article-title":"Single cell expression analysis reveals anatomical and cell cycle-dependent transcriptional shifts during heart development","volume":"146","author":"Li","year":"","journal-title":"Development"},{"key":"B55","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1016\/j.devcel.2016.10.014","article-title":"Transcriptomic profiling maps anatomically patterned subpopulations among single embryonic cardiac cells","volume":"39","author":"Li","year":"2016","journal-title":"Dev. Cell"},{"key":"B56","doi-asserted-by":"publisher","first-page":"eabk2432","DOI":"10.1126\/science.abk2432","article-title":"Fly cell atlas: A single-nucleus transcriptomic atlas of the adult fruit fly","volume":"375","author":"Li","year":"","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2507","DOI":"10.1093\/eurheartj\/ehz305","article-title":"Single-cell transcriptome analyses reveal novel targets modulating cardiac neovascularization by resident endothelial cells following myocardial infarction","volume":"40","author":"Li","year":"","journal-title":"Eur. Heart J."},{"key":"B58","doi-asserted-by":"publisher","first-page":"11295","DOI":"10.3390\/ijms222011295","article-title":"The genetics of diabetes: What we can learn from Drosophila","volume":"22","author":"Liguori","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B59","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/s41586-020-2797-4","article-title":"Cells of the adult human heart","volume":"588","author":"Litvinukova","year":"2020","journal-title":"Nature"},{"key":"B60","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cmet.2006.05.013","article-title":"Activated FOXO-mediated insulin resistance is blocked by reduction of TOR activity","volume":"4","author":"Luong","year":"2006","journal-title":"Cell Metab."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1101\/gad.9.13.1654","article-title":"Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5","volume":"9","author":"Lyons","year":"1995","journal-title":"Genes Dev."},{"key":"B62","doi-asserted-by":"publisher","first-page":"e14348","DOI":"10.1371\/journal.pone.0014348","article-title":"Arrhythmia caused by a Drosophila tropomyosin mutation is revealed using a novel optical coherence tomography instrument","volume":"5","author":"Ma","year":"2010","journal-title":"PLoS One"},{"key":"B63","doi-asserted-by":"publisher","first-page":"e1008639","DOI":"10.1371\/journal.pgen.1008639","article-title":"Novel frameshift variant in MYL2 reveals molecular differences between dominant and recessive forms of hypertrophic cardiomyopathy","volume":"16","author":"Manivannan","year":"2020","journal-title":"PLoS Genet."},{"key":"B64","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.accreview.2003.12.072","article-title":"NKX2.5 mutations in patients with congenital heart disease","volume":"13","author":"McElhinney","year":"2004","journal-title":"Acc. Curr. J. Rev."},{"key":"B65","doi-asserted-by":"publisher","first-page":"dmm048931","DOI":"10.1242\/dmm.048931","article-title":"ELAC2\/RNaseZ-linked cardiac hypertrophy in Drosophila melanogaster","volume":"14","author":"Migunova","year":"2021","journal-title":"Dis. Model. Mech."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e1003175","DOI":"10.1371\/journal.pgen.1003175","article-title":"A Drosophila model of high sugar diet-induced cardiomyopathy","volume":"9","author":"Na","year":"2013","journal-title":"PLoS Genet."},{"key":"B67","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.cell.2010.02.023","article-title":"A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function","volume":"141","author":"Neely","year":"2010","journal-title":"Cell"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3943","DOI":"10.1073\/pnas.0609278104","article-title":"KCNQ potassium channel mutations cause cardiac arrhythmias in Drosophila that mimic the effects of aging","volume":"104","author":"Ocorr","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.1126\/science.1132292","article-title":"Gene regulatory networks in the evolution and development of the heart","volume":"313","author":"Olson","year":"2006","journal-title":"Science"},{"key":"B70","doi-asserted-by":"publisher","first-page":"dmm033811","DOI":"10.1242\/dmm.033811","article-title":"Identification of cardioprotective drugs by medium-scale in vivo pharmacological screening on a Drosophila cardiac model of Friedreich\u2019s ataxia","volume":"11","author":"Palandri","year":"2018","journal-title":"Dis. Model. Mech."},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.17196.1","article-title":"mTOR as a central regulator of lifespan and aging","volume":"8","author":"Papadopoli","year":"2019","journal-title":"F1000Res"},{"key":"B72","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1290\/1071-2690(2001)037<0445:aivmfr>2.0.co;2","article-title":"An in vitro method for recording the electrical activity of the isolated heart of the adult Drosophila melanogaster","volume":"37","author":"Papaefthmiou","year":"2001","journal-title":"Vitro Cell. Dev. Biol. Anim."},{"key":"B73","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1016\/s0092-8674(04)00405-2","article-title":"Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block","volume":"117","author":"Pashmforoush","year":"2004","journal-title":"Cell"},{"key":"B74","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1161\/hh1001.090857","article-title":"Age-associated cardiac dysfunction in Drosophila melanogaster","volume":"88","author":"Paternostro","year":"2001","journal-title":"Circ. Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"H296","DOI":"10.1152\/ajpheart.00387.2021","article-title":"Analysis of Drosophila cardiac hypertrophy by microcomputerized tomography for genetic dissection of heart growth mechanisms","volume":"322","author":"Petersen","year":"2022","journal-title":"Am. J. Physiology-Heart Circulatory Physiology"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1161\/CIRCRESAHA.120.316101","article-title":"Obesity phenotypes, diabetes, and cardiovascular diseases","volume":"126","author":"Pich\u00e9","year":"2020","journal-title":"Circ. Res."},{"key":"B77","doi-asserted-by":"publisher","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":"B78","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/s41436-018-0408-7","article-title":"Insights into genetics, human biology and disease gleaned from family based genomic studies","volume":"21","author":"Posey","year":"2019","journal-title":"Genet. Med."},{"key":"B79","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1111\/j.1582-4934.2012.01529.x","article-title":"Probing the polygenic basis of cardiomyopathies in Drosophila","volume":"16","author":"Qian","year":"2012","journal-title":"J. Cell. Mol. Med."},{"key":"B80","doi-asserted-by":"publisher","first-page":"19833","DOI":"10.1073\/pnas.0808705105","article-title":"Transcription factor neuromancer\/TBX20 is required for cardiac function in Drosophila with implications for human heart disease","volume":"105","author":"Qian","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B81","doi-asserted-by":"publisher","first-page":"A79","DOI":"10.1016\/j.jacc.2006.09.014","article-title":"The genetic bases of cardiomyopathies","volume":"48","author":"Richard","year":"2006","journal-title":"J. Am. Coll. Cardiol."},{"key":"B82","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3390\/jcdd3020015","article-title":"On the morphology of the Drosophila heart","volume":"3","author":"Rotstein","year":"2016","journal-title":"J. Cardiovasc. Dev. Dis."},{"key":"B83","doi-asserted-by":"publisher","first-page":"3954","DOI":"10.1093\/hmg\/ddz213","article-title":"Model system identification of novel congenital heart disease gene candidates: Focus on RPL13","volume":"28","author":"Schroeder","year":"2019","journal-title":"Hum. Mol. Genet."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1038\/ng.3627","article-title":"Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing","volume":"48","author":"Sifrim","year":"2016","journal-title":"Nat. Genet."},{"key":"B85","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1016\/j.celrep.2017.12.072","article-title":"Single-cell transcriptional profiling reveals cellular diversity and intercommunication in the mouse heart","volume":"22","author":"Skelly","year":"2018","journal-title":"Cell Rep."},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3390\/cells10113078","article-title":"Drosophila heart as a model for cardiac development and diseases","volume":"10","author":"Souidi","year":"2021","journal-title":"Cells"},{"key":"B87","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/j.1474-9726.2008.00367.x","article-title":"Dystrophin deficiency in Drosophila reduces lifespan and causes a dilated cardiomyopathy phenotype","volume":"7","author":"Taghli-Lamallem","year":"2008","journal-title":"Aging Cell"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1269","DOI":"10.1242\/dev.126.6.1269","article-title":"The cardiac homeobox gene Csx\/Nkx2.5 lies genetically upstream of multiple genes essential for heart development","volume":"126","author":"Tanaka","year":"1999","journal-title":"Development"},{"key":"B89","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1387\/ijdb.120111ap","article-title":"In vivo imaging of Drosophila wing heart development during pupal stages","volume":"57","author":"T\u00f6gel","year":"2013","journal-title":"Int. J. Dev. Biol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ydbio.2008.02.043","article-title":"The Drosophila wing hearts originate from pericardial cells and are essential for wing maturation","volume":"318","author":"T\u00f6gel","year":"2008","journal-title":"Dev. Biol."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.045401","article-title":"Transcriptional and cellular diversity of the human heart","volume":"2020","author":"Tucker","year":"2020","journal-title":"Circulation"},{"key":"B92","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1242\/dmm.023762","article-title":"Drosophila tools and assays for the study of human diseases","volume":"9","author":"Ugur","year":"2016","journal-title":"Dis. Model. Mech."},{"key":"B93","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/s41431-018-0281-5","article-title":"Heterozygous loss-of-function variants of MEIS2 cause a triad of palatal defects, congenital heart defects, and intellectual disability","volume":"27","author":"Verheije","year":"2019","journal-title":"Eur. J. Hum. Genet."},{"key":"B94","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1038\/s41556-019-0336-z","article-title":"A single-cell transcriptional roadmap for cardiopharyngeal fate diversification","volume":"21","author":"Wang","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"e017731","DOI":"10.1161\/JAHA.120.017731","article-title":"Genetic causes of cardiomyopathy in children: First results from the pediatric cardiomyopathy genes study","volume":"10","author":"Ware","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"B96","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.devcel.2020.01.023","article-title":"Functional heterogeneity within the developing zebrafish epicardium","volume":"52","author":"Weinberger","year":"2020","journal-title":"Dev. Cell"},{"key":"B97","doi-asserted-by":"publisher","first-page":"542","DOI":"10.1111\/j.1474-9726.2009.00504.x","article-title":"d4eBP acts downstream of both dTOR and dFoxo to modulate cardiac functional aging in Drosophila","volume":"8","author":"Wessells","year":"2009","journal-title":"Aging Cell"},{"key":"B98","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1038\/ng1476","article-title":"Insulin regulation of heart function in aging fruit flies","volume":"36","author":"Wessells","year":"2004","journal-title":"Nat. Genet."},{"key":"B99","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1073\/pnas.0507359103","article-title":"Drosophila as a model for the identification of genes causing adult human heart disease","volume":"103","author":"Wolf","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B100","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/j.ddmod.2009.02.002","article-title":"Drosophila melanogaster as a model system for genetics of postnatal cardiac function","volume":"5","author":"Wolf","year":"2008","journal-title":"Drug Discov. Today Dis. Models"},{"key":"B101","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1242\/dmm.011361","article-title":"Raf-mediated cardiac hypertrophy in adult Drosophila","volume":"6","author":"Yu","year":"2013","journal-title":"Dis. Model. Mech."},{"key":"B102","doi-asserted-by":"publisher","first-page":"e1000969","DOI":"10.1371\/journal.pgen.1000969","article-title":"Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila","volume":"6","author":"Yu","year":"2010","journal-title":"PLoS Genet."},{"key":"B103","doi-asserted-by":"publisher","first-page":"4977","DOI":"10.1038\/s41467-018-07451-z","article-title":"Heart enhancers with deeply conserved regulatory activity are established early in zebrafish development","volume":"9","author":"Yuan","year":"2018","journal-title":"Nat. Commun."},{"key":"B104","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nature12141","article-title":"De novo mutations in histone-modifying genes in congenital heart disease","volume":"498","author":"Zaidi","year":"2013","journal-title":"Nature"},{"key":"B105","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s12915-021-01106-0","article-title":"Stop codon readthrough alters the activity of a POU\/Oct transcription factor during Drosophila development","volume":"19","author":"Zhao","year":"2021","journal-title":"BMC Biol."},{"key":"B106","doi-asserted-by":"publisher","first-page":"e22617","DOI":"10.7554\/eLife.22617","article-title":"High throughput in vivo functional validation of candidate congenital heart disease genes in Drosophila","volume":"6","author":"Zhu","year":"","journal-title":"Elife"},{"key":"B107","doi-asserted-by":"publisher","first-page":"e2350","DOI":"10.21769\/BioProtoc.2350","article-title":"Validating candidate congenital heart disease genes in Drosophila","volume":"7","author":"Zhu","year":"","journal-title":"Bio Protoc."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1182610\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T11:29:20Z","timestamp":1684322960000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1182610\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,12]]},"references-count":107,"alternative-id":["10.3389\/fphys.2023.1182610"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1182610","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,12]]},"article-number":"1182610"}}