{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:07:03Z","timestamp":1762420023113,"version":"build-2065373602"},"reference-count":67,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instituto de Salud Carlos III (ISCIII) Health Research Fund","award":["PI13\/02278"],"award-info":[{"award-number":["PI13\/02278"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["423\/C\/2015"],"award-info":[{"award-number":["423\/C\/2015"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"name":"IdISBA, the program TALENT-Plus TECH, and the sustainable tourism tax from the Govern de les Illes Balears"},{"name":"JoTRES Program\u2014Young Talents in Health Research or SOIB Qualificats Sector P\u00fablic (UIB) i Entitats Locals"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Congenital heart defects (CHDs) occur in 50\u201375% of patients with 22q11.2 deletion syndrome (22q11.2DS), ranging from mild to severe manifestations. The genetic and environmental factors contributing to variable CHD phenotypes in 22q11.2DS are largely unknown. In this study, we used a mouse model of 22q11.2DS, termed Df1\/+, to evaluate the effect of maternal vitamin A (VitA) dietary imbalance (supplementation or deficiency) on the incidence of aortic arch defects (AADs), which is a common type of CHD observed in both 22q11.2DS patients and Df1\/+ mouse embryos. While most groups showed a previously observed 30% AAD incidence, two groups exhibited significantly higher rates: (1) Df1\/+ embryos from WT mothers on a VitA-Supl diet (51% AADs) and (2) Df1\/+ embryos from Df1\/+ mothers on a VitA-Def diet (45% AADs). Thus, a low or high maternal VitA diet can increase the frequency of AADs in embryos depending on the maternal genotype. Transcriptomic analysis of the hearts of these high-risk embryos at embryonic day (E)18.5 revealed downregulation of key genes (Hdac3, Ptgds, Sirt5, Pfkm, and Lclat1) associated with energy metabolism pathways, such as oxidative phosphorylation and glycolysis, suggesting impaired cardiac recovery mechanisms. In conclusion, our findings demonstrate that altered VitA exposure can exacerbate AAD incidence in a maternal-genotype-dependent manner, highlighting the complex interplay between embryonic and maternal genetic background and environmental factors in CHDs associated with 22q11.2DS.<\/jats:p>","DOI":"10.3390\/ijms262110595","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:23:59Z","timestamp":1761873839000},"page":"10595","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Maternal Genotype and Dietary Vitamin A Modify Aortic Arch Phenotypes in a Mouse Model of 22q11DS"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4795-316X","authenticated-orcid":false,"given":"Emilia","family":"Amengual-Cladera","sequence":"first","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Vict\u00f2ria","family":"Llull-Alberti","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4229-2737","authenticated-orcid":false,"given":"Marc","family":"Ventayol-Guirado","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3404-0241","authenticated-orcid":false,"given":"Juan Antonio","family":"Jimenez-Barcelo","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jairo Enrique","family":"Rocha","sequence":"additional","affiliation":[{"name":"Grup de Biologia Computacional i Bioinform\u00e0tica (BIOCOM), Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"},{"name":"Grup de Biologia Computacional i Bioinform\u00e0tica (BIOCOM), Universitat de les Illes Balears, 07122 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josep","family":"Muncunill","sequence":"additional","affiliation":[{"name":"Genomics and Bioinformatics Platform, Balearic Islands Health Research Institute (IdISBa), University Hospital Son Espases, 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0402-286X","authenticated-orcid":false,"given":"Jessica","family":"Hernandez-Rodriguez","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"},{"name":"Molecular Diagnostics and Clinical Genetics Unit (UDMGC), Hospital Universitari Son Espases, Carretera de Valldemossa 79, 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6942-0829","authenticated-orcid":false,"given":"Daniela","family":"Medina-Ch\u00e1vez","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5375-7195","authenticated-orcid":false,"given":"Elionor","family":"Lynton-Pons","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Sureda-Horrach","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor Jose","family":"Asensio","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"},{"name":"Molecular Diagnostics and Clinical Genetics Unit (UDMGC), Hospital Universitari Son Espases, Carretera de Valldemossa 79, 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Ruiz-Guerra","sequence":"additional","affiliation":[{"name":"Grupo Neurobiolog\u00eda, University of Balearic Islands (UIB), 07122 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5460-0763","authenticated-orcid":false,"given":"Albert","family":"Tubau","sequence":"additional","affiliation":[{"name":"Servicio de Ginecolog\u00eda y Obstetricia, Hospital Universitario Son Ll\u00e0tzer, 07198 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel","family":"Juan-Clar","sequence":"additional","affiliation":[{"name":"Servicio de Ginecolog\u00eda y Obstetricia, Hospital Universitario Son Ll\u00e0tzer, 07198 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-7085-7317","authenticated-orcid":false,"given":"Marchesa","family":"Bilio","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics Adriano Buzzati-Traverso, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernice","family":"Morrow","sequence":"additional","affiliation":[{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5735-8335","authenticated-orcid":false,"given":"Crist\u00f3fol","family":"Vives-Bauz\u00e0","sequence":"additional","affiliation":[{"name":"Grupo Neurobiolog\u00eda, University of Balearic Islands (UIB), 07122 Palma, Balearic Islands, Spain"},{"name":"Grup de Neurobiologia, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3681-0251","authenticated-orcid":false,"given":"Gabriella","family":"Lania","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics Adriano Buzzati-Traverso, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Illingworth","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biology, University of Salerno, 84084 Fisciano, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5330-0256","authenticated-orcid":false,"given":"Antonio","family":"Baldini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University Federico II, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9374-1219","authenticated-orcid":false,"given":"Alexander Damian","family":"Heine-Su\u00f1er","sequence":"additional","affiliation":[{"name":"Genomics of Health Research Group, Institute of Health Sciences Research of the Balearic Islands (IdISBa), 07120 Palma, Balearic Islands, Spain"},{"name":"Grupo Neurobiolog\u00eda, University of Balearic Islands (UIB), 07122 Palma, Balearic Islands, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1016\/S0735-1097(02)01886-7","article-title":"The incidence of congenital heart disease","volume":"39","author":"Hoffman","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/nature06801","article-title":"The developmental genetics of congenital heart disease","volume":"451","author":"Bruneau","year":"2008","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1161\/CIRCULATIONAHA.110.958405","article-title":"Congenital heart defects in Europe: Prevalence and perinatal mortality, 2000 to 2005","volume":"123","author":"Dolk","year":"2011","journal-title":"Circulation"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41569-021-00587-4","article-title":"Genomic frontiers in congenital heart disease","volume":"19","author":"Morton","year":"2022","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2419992122","DOI":"10.1073\/pnas.2419992122","article-title":"Recessive genetic contribution to congenital heart disease in 5,424 probands","volume":"122","author":"Dong","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2420343122","DOI":"10.1073\/pnas.2420343122","article-title":"Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes","volume":"122","author":"Sierant","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"a013946","DOI":"10.1101\/cshperspect.a013946","article-title":"Insights into the genetic structure of congenital heart disease from human and murine studies on monogenic disorders","volume":"4","author":"Prendiville","year":"2014","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.21037\/tp-21-297","article-title":"Genetics of congenital heart disease: A narrative review of recent advances and clinical implications","volume":"10","author":"Yasuhara","year":"2021","journal-title":"Transl. Pediatr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1002\/pd.4613","article-title":"Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies","volume":"35","author":"Grati","year":"2015","journal-title":"Prenat. Diagn."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/hmg\/8.7.1157","article-title":"A Common Molecular Basis for Rearrangement Disorders on Chromosome 22q11","volume":"8","author":"Edelmann","year":"1999","journal-title":"Hum. Mol. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1086\/302343","article-title":"Low-copy repeats mediate the common 3-Mb deletion in patients with velo-cardio-facial syndrome","volume":"64","author":"Edelmann","year":"1999","journal-title":"Am. J. Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/hmg\/9.4.489","article-title":"Chromosome 22-specific low copy repeats and the 22q11.2 deletion syndrome: Genomic organization and deletion endpoint analysis","volume":"9","author":"Shaikh","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/S0092-8674(01)00247-1","article-title":"TBX1 is responsible for cardiovascular defects in velo-cardio-facial\/DiGeorge syndrome","volume":"104","author":"Merscher","year":"2001","journal-title":"Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1093\/hmg\/10.9.997","article-title":"Recovery from arterial growth delay reduces penetrance of cardiovascular defects in mice deleted for the DiGeorge syndrome region","volume":"10","author":"Lindsay","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1038\/85845","article-title":"DiGeorge syndrome phenotype in mice mutant for the T-box gene, Tbx1","volume":"27","author":"Jerome","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/bs.ctdb.2016.08.002","article-title":"Tbx1: Transcriptional and Developmental Functions","volume":"122","author":"Baldini","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.ajhg.2014.12.025","article-title":"Mouse and human CRKL is dosage sensitive for cardiac outflow tract formation","volume":"96","author":"Racedo","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1002\/ajmg.c.31774","article-title":"22Q11.2 Deletion Syndrome and Congenital Heart Disease","volume":"184","author":"Goldmuntz","year":"2020","journal-title":"Am. J. Med. Genet. Part C Semin. Med. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nm819","article-title":"VEGF: A modifier of the del22q11 (DiGeorge) syndrome?","volume":"9","author":"Stalmans","year":"2003","journal-title":"Nat. Med."},{"key":"ref_20","first-page":"229","article-title":"Role of the vascular endothelial growth factor isoforms in retinal angiogenesis and DiGeorge syndrome","volume":"67","author":"Stalmans","year":"2005","journal-title":"Verh. K. Acad. Geneeskd. Belg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ajhg.2019.11.010","article-title":"Complete Sequence of the 22q11.2 Allele in 1,053 Subjects with 22q11.2 Deletion Syndrome Reveals Modifiers of Conotruncal Heart Defects","volume":"106","author":"Zhao","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41525-023-00363-y","article-title":"Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS","volume":"8","author":"Zhao","year":"2023","journal-title":"Npj Genom. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.ajhg.2015.10.013","article-title":"Histone Modifier Genes Alter Conotruncal Heart Phenotypes in 22q11.2 Deletion Syndrome","volume":"97","author":"Guo","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/43900","article-title":"Congenital heart disease in mice deficient for the DiGeorge syndrome region","volume":"401","author":"Lindsay","year":"1999","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/s11689-015-9113-x","article-title":"Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms","volume":"7","author":"Guna","year":"2015","journal-title":"J. Neurodev. Disord."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s11689-019-9267-z","article-title":"In the line-up: Deleted genes associated with DiGeorge\/22q11.2 deletion syndrome: Are they all suspects?","volume":"11","author":"Motahari","year":"2019","journal-title":"J. Neurodev. Disord."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/35065105","article-title":"Tbx1 haploinsufficiency in the DiGeorge syndrome region causes aortic arch defects in mice","volume":"410","author":"Lindsay","year":"2001","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"dmm036491","DOI":"10.1242\/dmm.036491","article-title":"The ubiquitin ligase HECTD1 promotes retinoic acid signaling required for development of the aortic arch","volume":"12","author":"Sugrue","year":"2019","journal-title":"DMM Dis. Model. Mech."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e23326","DOI":"10.1002\/dvg.23326","article-title":"Reduced maternal vitamin A status increases the incidence of normal aortic arch variants","volume":"57","author":"Sugrue","year":"2019","journal-title":"Genesis"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1073\/pnas.0437920100","article-title":"Decreased embryonic retinoic acid synthesis results in a DiGeorge syndrome phenotype in newborn mice","volume":"100","author":"Vermot","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1161\/CIRCRESAHA.109.205732","article-title":"Decreased levels of embryonic retinoic acid synthesis accelerate recovery from arterial growth delay in a mouse model of digeorge syndrome","volume":"106","author":"Ryckebusch","year":"2010","journal-title":"Circ. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1002\/bdr2.1709","article-title":"Variations in maternal vitamin A intake modifies phenotypes in a mouse model of 22q11.2 deletion syndrome","volume":"112","author":"Yitsege","year":"2020","journal-title":"Birth Defects Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.taap.2003.09.031","article-title":"Gene-nutrient interactions: Importance of folates and retinoids during early embryogenesis","volume":"198","author":"Finnell","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"390","DOI":"10.2174\/1389202915666140716175634","article-title":"Congenital Heart Disease: The Crossroads of Genetics, Epigenetics and Environment","volume":"15","author":"Vecoli","year":"2014","journal-title":"Curr. Genom."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kolmaga, A., Trafalska, E., Gaszy\u0144ska, E., Gawron-Skarbek, A., Witkowski, S., Murlewska, J., Respondek-Liberska, M., and Strzelecka, I. (2025). Vitamin D and LC-PUFA and the Presence of Fetal Heart Defects\u2014A Further Part of a Case-Control Study. Nutrients, 17.","DOI":"10.3390\/nu17010018"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e039684","DOI":"10.1161\/JAHA.124.039684","article-title":"Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects","volume":"14","author":"McMullan","year":"2025","journal-title":"J. Am. Heart Assoc."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Graham, A., Hikspoors, J.P.J.M., Lamers, W.H., Anderson, R.H., and Bamforth, S.D. (2023). Morphogenetic processes in the development and evolution of the arteries of the pharyngeal arches: Their relations to congenital cardiovascular malformations. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1259175"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1046\/j.1469-7580.2002.00071.x","article-title":"Development of pharyngeal arch arteries in early mouse embryo","volume":"201","author":"Hiruma","year":"2002","journal-title":"J. Anat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0012-1606(03)00112-X","article-title":"Heart development: Molecular insights into cardiac specification and early morphogenesis","volume":"258","author":"Brand","year":"2003","journal-title":"Dev. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Kodo, K., Uchida, K., and Yamagishi, H. (2021). Genetic and Cellular Interaction During Cardiovascular Development Implicated in Congenital Heart Diseases. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.653244"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Erhardt, S., Zheng, M., Zhao, X., Le, T.P., Findley, T.O., and Wang, J. (2021). The Cardiac Neural Crest Cells in Heart Development and Congenital Heart Defects. J. Cardiovasc. Dev. Dis., 8.","DOI":"10.3390\/jcdd8080089"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/35075590","article-title":"Linkage disequilibrium in the human genome","volume":"411","author":"Reich","year":"2001","journal-title":"Nature"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4605","DOI":"10.1242\/dev.129.19.4605","article-title":"A genetic link between Tbx1 and fibroblast growth factor signaling","volume":"129","author":"Vitelli","year":"2002","journal-title":"Development"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.devcel.2005.12.002","article-title":"Dose-dependent interaction of Tbx1 and Crkl and locally aberrant RA signaling in a model of del22q11 syndrome","volume":"10","author":"Guris","year":"2006","journal-title":"Dev. Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1093\/hmg\/ddm291","article-title":"In vivo response to high-resolution variation of Tbx1 mRNA dosage","volume":"17","author":"Zhang","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_47","first-page":"3301","article-title":"Great vessel development requires biallelic expression of Chd7 and Tbx1 in pharyngeal ectoderm in mice","volume":"119","author":"Randall","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3173","DOI":"10.1242\/dev.028902","article-title":"Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in thepharyngeal ectoderm","volume":"136","author":"Calmont","year":"2009","journal-title":"Development"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1161\/CIRCRESAHA.112.270223","article-title":"Tbx1 genetically interacts with the transforming growth factor-\u03b2\/bone morphogenetic protein inhibitor Smad7 during great vessel remodeling","volume":"112","author":"Papangeli","year":"2013","journal-title":"Circ. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Anderson, R.H., and Bamforth, S.D. (2022). Morphogenesis of the Mammalian Aortic Arch Arteries. Front. Cell Dev. Biol., 10.","DOI":"10.3389\/fcell.2022.892900"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"11428","DOI":"10.1073\/pnas.201127298","article-title":"Genetic factors are major determinants of phenotypic variability in a mouse model of the DiGeorge\/del22q11 syndromes","volume":"98","author":"Taddei","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1161\/CIRCRESAHA.109.215319","article-title":"DiGeorge Syndrome, Tbx1, and Retinoic Acid Signaling Come Full Circle","volume":"106","author":"Yutzey","year":"2010","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1002\/dvdy.20268","article-title":"Retinoic acid down-regulates Tbx1 expression in vivo and in vitro","volume":"232","author":"Roberts","year":"2005","journal-title":"Dev. Dyn."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41392-024-02069-8","article-title":"The molecular mechanisms of cardiac development and related diseases","volume":"9","author":"Li","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e49752","DOI":"10.15252\/embr.201949752","article-title":"Stimulation of glycolysis promotes cardiomyocyte proliferation after injury in adult zebrafish","volume":"21","author":"Fukuda","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s00395-023-01018-w","article-title":"The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches","volume":"118","author":"Chen","year":"2023","journal-title":"Basic Res. Cardiol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Hershberger, K.A., Abraham, D.M., Martin, A.S., Mao, L., Liu, J., Gu, H., Locasale, J.W., and Hirschey, M.D. (2017). Sirtuin 5 is required for mouse survival in response to cardiac pressure overload. J. Biol. Chem., 292.","DOI":"10.1074\/jbc.M117.809897"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1016\/j.ymthe.2021.06.007","article-title":"Cardiolipin remodeling by ALCAT1 links hypoxia to coronary artery disease by promoting mitochondrial dysfunction","volume":"29","author":"Jia","year":"2021","journal-title":"Mol. Ther."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-019-0299-y","article-title":"Prostaglandin D2 stimulates phenotypic changes in vascular smooth muscle cells","volume":"51","author":"Lee","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e13731","DOI":"10.1111\/cpr.13731","article-title":"HDAC3 in action: Expanding roles in inflammation and inflammatory diseases","volume":"58","author":"He","year":"2025","journal-title":"Cell Prolif."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Urvalek, A.M., and Gudas, L.J. (2014). Retinoic Acid and Histone Deacetylases Regulate Epigenetic Changes in Embryonic Stem Cells. J. Biol. Chem., 289.","DOI":"10.1074\/jbc.M114.556555"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1161\/CIRCRESAHA.111.255067","article-title":"Histone deacetylase 3 regulates smooth muscle differentiation in neural crest cells and development of the cardiac outflow tract","volume":"109","author":"Singh","year":"2011","journal-title":"Circ. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3588","DOI":"10.1172\/JCI35847","article-title":"Maintenance of cardiac energy metabolism by histone deacetylase 3 in mice","volume":"118","author":"Montgomery","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Sun, Z., Singh, N., Mullican, S.E., Everett, L.J., Li, L., Yuan, L., Liu, X., Epstein, J.A., and Lazar, M.A. (2011). Diet-induced Lethality Due to Deletion of the Hdac3 Gene in Heart and Skeletal Muscle. J. Biol. Chem., 286.","DOI":"10.1074\/jbc.M111.277707"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3563","DOI":"10.1242\/dev.129.15.3563","article-title":"Embryonic retinoic acid synthesis is required for forelimb growth and anteroposterior patterning in the mouse","volume":"129","author":"Niederreither","year":"2002","journal-title":"Development"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS A J. Integr. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10595\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T09:03:03Z","timestamp":1762419783000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/21\/10595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,30]]},"references-count":67,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262110595"],"URL":"https:\/\/doi.org\/10.3390\/ijms262110595","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,10,30]]}}}