{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T16:18:06Z","timestamp":1761581886737,"version":"3.44.0"},"reference-count":55,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,2,1]],"date-time":"2021-02-01T00:00:00Z","timestamp":1612137600000},"content-version":"vor","delay-in-days":366,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL135582"],"award-info":[{"award-number":["HL135582"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013899","name":"M.S.I. Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013899","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Developmental Biology"],"published-print":{"date-parts":[[2020,2]]},"DOI":"10.1016\/j.ydbio.2019.10.022","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T11:12:24Z","timestamp":1572001944000},"page":"88-97","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"title":["FRS2\u03b1-dependent cell fate transition during endocardial cushion morphogenesis"],"prefix":"10.1016","volume":"458","author":[{"given":"Dongying","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Kofler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yidong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Simons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ydbio.2019.10.022_bib1","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.jacc.2017.07.734","article-title":"Effect of losartan on mitral valve changes after myocardial infarction","volume":"70","author":"Bartko","year":"2017","journal-title":"J.\u00a0Am. Coll. Cardiol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib2","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1161\/CIRCRESAHA.116.309598","article-title":"CD45 expression in mitral valve endothelial cells after myocardial infarction","volume":"119","author":"Bischoff","year":"2016","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2019.10.022_bib3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1006\/dbio.2002.0731","article-title":"Temporal and distinct TGFbeta ligand requirements during mouse and avian endocardial cushion morphogenesis","volume":"248","author":"Camenisch","year":"2002","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib4","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1006\/dbio.2002.0731","article-title":"Temporal and distinct TGF\u03b2 ligand requirements during mouse and avian endocardial cushion morphogenesis","volume":"248","author":"Camenisch","year":"2002","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib5","first-page":"363","article-title":"Chapter 6.1 - Molecular Regulation of Cushion Morphogenesis In:Heart Development and Regeneration","author":"Camenisch","year":"2010","journal-title":"Elsevier Inc."},{"key":"10.1016\/j.ydbio.2019.10.022_bib6","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.1016\/j.celrep.2012.10.021","article-title":"FGF regulates TGF-beta signaling and endothelial-to-mesenchymal transition via control of let-7 miRNA expression","volume":"2","author":"Chen","year":"2012","journal-title":"Cell Rep."},{"key":"10.1016\/j.ydbio.2019.10.022_bib7","doi-asserted-by":"crossref","first-page":"33407","DOI":"10.1038\/srep33407","article-title":"Fibroblast growth factor (FGF) signaling regulates transforming growth factor beta (TGFbeta)-dependent smooth muscle cell phenotype modulation","volume":"6","author":"Chen","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.ydbio.2019.10.022_bib8","doi-asserted-by":"crossref","first-page":"712","DOI":"10.15252\/emmm.201506181","article-title":"Smooth muscle FGF\/TGFbeta cross talk regulates atherosclerosis progression","volume":"8","author":"Chen","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ydbio.2019.10.022_bib9","doi-asserted-by":"crossref","first-page":"ra90","DOI":"10.1126\/scisignal.2005504","article-title":"Fibroblast growth factor receptor 1 is a key inhibitor of TGFbeta signaling in the endothelium","volume":"7","author":"Chen","year":"2014","journal-title":"Sci. Signal."},{"key":"10.1016\/j.ydbio.2019.10.022_bib10","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1073\/pnas.1404545111","article-title":"The docking protein FRS2alpha is a critical regulator of VEGF receptors signaling","volume":"111","author":"Chen","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ydbio.2019.10.022_bib11","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.2174\/1389450117666160502151308","article-title":"Future targets in endothelial biology: endothelial cell to mesenchymal transition","volume":"17","author":"Chen","year":"2016","journal-title":"Curr. Drug Targets"},{"key":"10.1016\/j.ydbio.2019.10.022_bib12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15252\/emmm.201505943","article-title":"When endothelial cells go rogue","volume":"8","author":"Chen","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.ydbio.2019.10.022_bib13","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/MOL.0000000000000542","article-title":"Fibroblast growth factor-transforming growth factor beta dialogues, endothelial cell to mesenchymal transition, and atherosclerosis","volume":"29","author":"Chen","year":"2018","journal-title":"Curr. Opin. Lipidol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib14","doi-asserted-by":"crossref","first-page":"15980","DOI":"10.1074\/jbc.M809399200","article-title":"FRS2 via fibroblast growth factor receptor 1 is required for platelet-derived growth factor receptor beta-mediated regulation of vascular smooth muscle marker gene expression","volume":"284","author":"Chen","year":"2009","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.ydbio.2019.10.022_bib15","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1161\/CIRCULATIONAHA.108.846782","article-title":"Active adaptation of the tethered mitral valve: insights into a compensatory mechanism for functional mitral regurgitation","volume":"120","author":"Dal-Bianco","year":"2009","journal-title":"Circulation"},{"key":"10.1016\/j.ydbio.2019.10.022_bib16","doi-asserted-by":"crossref","first-page":"14361","DOI":"10.1038\/ncomms14361","article-title":"The molecular basis of endothelial cell plasticity","volume":"8","author":"Dejana","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2019.10.022_bib17","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1210\/endo.141.2.7298","article-title":"Potential involvement of FRS2 in insulin signaling","volume":"141","author":"Delahaye","year":"2000","journal-title":"Endocrinology"},{"key":"10.1016\/j.ydbio.2019.10.022_bib18","doi-asserted-by":"crossref","first-page":"11853","DOI":"10.1038\/ncomms11853","article-title":"Endothelial to mesenchymal transition is common in atherosclerotic lesions and is associated with plaque instability","volume":"7","author":"Evrard","year":"2016","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2019.10.022_bib19","doi-asserted-by":"crossref","first-page":"4105","DOI":"10.1128\/MCB.25.10.4105-4116.2005","article-title":"The docking protein FRS2alpha is an essential component of multiple fibroblast growth factor responses during early mouse development","volume":"25","author":"Gotoh","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib20","doi-asserted-by":"crossref","first-page":"8578","DOI":"10.1073\/pnas.161259898","article-title":"Critical role for the docking-protein FRS2 alpha in FGF receptor-mediated signal transduction pathways","volume":"98","author":"Hadari","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ydbio.2019.10.022_bib21","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1161\/01.RES.0000224114.65109.4e","article-title":"Extracellular matrix remodeling and organization in developing and diseased aortic valves","volume":"98","author":"Hinton","year":"2006","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2019.10.022_bib22","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1146\/annurev-physiol-012110-142145","article-title":"Heart valve structure and function in development and disease","volume":"73","author":"Hinton","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib23","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.ydbio.2007.12.028","article-title":"BMP-2 induces cell migration and periostin expression during atrioventricular valvulogenesis","volume":"315","author":"Inai","year":"2008","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib24","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1242\/dev.063495","article-title":"Partitioning the heart: mechanisms of cardiac septation and valve development","volume":"139","author":"Lin","year":"2012","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2019.10.022_bib25","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1002\/dvdy.20051","article-title":"Development of heart valve leaflets and supporting apparatus in chicken and mouse embryos","volume":"230","author":"Lincoln","year":"2004","journal-title":"Dev. Dynam."},{"key":"10.1016\/j.ydbio.2019.10.022_bib26","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1002\/dvdy.20980","article-title":"ColVa1 and ColXIa1 are required for myocardial morphogenesis and heart valve development","volume":"235","author":"Lincoln","year":"2006","journal-title":"Dev. Dynam."},{"key":"10.1016\/j.ydbio.2019.10.022_bib27","doi-asserted-by":"crossref","first-page":"3493","DOI":"10.1172\/JCI42666","article-title":"Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation","volume":"120","author":"Luna-Zurita","year":"2010","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.ydbio.2019.10.022_bib28","doi-asserted-by":"crossref","first-page":"5601","DOI":"10.1242\/dev.02156","article-title":"Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning","volume":"132","author":"Ma","year":"2005","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2019.10.022_bib29","doi-asserted-by":"crossref","first-page":"3355","DOI":"10.1172\/JCI35298","article-title":"The FGF system has a key role in regulating vascular integrity","volume":"118","author":"Murakami","year":"2008","journal-title":"J.\u00a0Clin. Investig."},{"key":"10.1016\/j.ydbio.2019.10.022_bib30","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1007\/s00109-009-0463-2","article-title":"Regulation of vascular integrity","volume":"87","author":"Murakami","year":"2009","journal-title":"J.\u00a0Mol. Med. (Berl.)"},{"key":"10.1016\/j.ydbio.2019.10.022_bib31","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1002\/dvg.20335","article-title":"A\u00a0global double-fluorescent Cre reporter mouse","volume":"45","author":"Muzumdar","year":"2007","journal-title":"Genesis"},{"key":"10.1016\/j.ydbio.2019.10.022_bib32","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ydbio.2008.01.003","article-title":"Periostin regulates atrioventricular valve maturation","volume":"316","author":"Norris","year":"2008","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib33","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1128\/MCB.20.3.979-989.2000","article-title":"FRS2 proteins recruit intracellular signaling pathways by binding to diverse targets on fibroblast growth factor and nerve growth factor receptors","volume":"20","author":"Ong","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1002\/wdev.176","article-title":"The fibroblast growth factor signaling pathway","volume":"4","author":"Ornitz","year":"2015","journal-title":"Wiley Interdiscipl. Rev. Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib35","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/s41419-018-0442-z","article-title":"Myocardial Bmp2 gain causes ectopic EMT and promotes cardiomyocyte proliferation and immaturity","volume":"9","author":"Prados","year":"2018","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.ydbio.2019.10.022_bib36","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/35002607","article-title":"The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans","volume":"403","author":"Reinhart","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2019.10.022_bib37","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/0012-1606(83)90010-6","article-title":"Invasion of mesenchyme into three-dimensional collagen gels: a regional and temporal analysis of interaction in embryonic heart tissue","volume":"95","author":"Runyan","year":"1983","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib38","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1126\/science.aat3470","article-title":"A\u00a0unifying concept in vascular health and disease","volume":"360","author":"Schwartz","year":"2018","journal-title":"Science"},{"key":"10.1016\/j.ydbio.2019.10.022_bib39","doi-asserted-by":"crossref","first-page":"18604","DOI":"10.1073\/pnas.0900635106","article-title":"T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfbeta2 expression and endocardial cushion formation","volume":"106","author":"Shirai","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ydbio.2019.10.022_bib40","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1161\/CIRCRESAHA.107.159517","article-title":"Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart","volume":"102","author":"Snider","year":"2008","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2019.10.022_bib41","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S0012-1606(03)00158-1","article-title":"Loss of distinct arterial and venous boundaries in mice lacking endoglin, a vascular-specific TGFbeta coreceptor","volume":"261","author":"Sorensen","year":"2003","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib42","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ydbio.2008.07.038","article-title":"Signaling via the Tgf-beta type I receptor Alk5 in heart development","volume":"322","author":"Sridurongrit","year":"2008","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib43","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1096\/fj.01-0835fje","article-title":"Fibroblast growth factor receptor substrate 2 participates in vascular endothelial growth factor-induced signaling","volume":"16","author":"Stoletov","year":"2002","journal-title":"FASEB J."},{"key":"10.1016\/j.ydbio.2019.10.022_bib44","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.ydbio.2004.01.045","article-title":"Bone morphogenetic protein-2 can mediate myocardial regulation of atrioventricular cushion mesenchymal cell formation in mice","volume":"269","author":"Sugi","year":"2004","journal-title":"Dev. Biol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib45","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.cell.2010.02.007","article-title":"Lin28: a microRNA regulator with a macro role","volume":"140","author":"Viswanathan","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.ydbio.2019.10.022_bib46","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1161\/CIRCRESAHA.111.259960","article-title":"Endocardial and epicardial epithelial to mesenchymal transitions in heart development and disease","volume":"110","author":"von Gise","year":"2012","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2019.10.022_bib47","first-page":"73","article-title":"FRS2 alpha: at the center of FGF signaling","author":"Wang","year":"2017","journal-title":"Fibroblast Growth Factors: Biol. Clin. Appl. FGF Biol. Ther."},{"key":"10.1016\/j.ydbio.2019.10.022_bib48","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/nature09002","article-title":"Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis","volume":"465","author":"Wang","year":"2010","journal-title":"Nature"},{"key":"10.1016\/j.ydbio.2019.10.022_bib49","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/path.4814","article-title":"Fine-tuning vascular fate during endothelial-mesenchymal transition","volume":"241","author":"Xiao","year":"2017","journal-title":"J.\u00a0Pathol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib50","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1038\/s41467-018-08127-4","article-title":"Lin28 and let-7 regulate the timing of cessation of murine nephrogenesis","volume":"10","author":"Yermalovich","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.ydbio.2019.10.022_bib51","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1002\/prot.24523","article-title":"Structural insights into FRS2alpha PTB domain recognition by neurotrophin receptor TrkB","volume":"82","author":"Zeng","year":"2014","journal-title":"Proteins"},{"key":"10.1016\/j.ydbio.2019.10.022_bib52","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1161\/CIRCRESAHA.110.225318","article-title":"The FGF-BMP signaling axis regulates outflow tract valve primordium formation by promoting cushion neural crest cell differentiation","volume":"107","author":"Zhang","year":"2010","journal-title":"Circ. Res."},{"key":"10.1016\/j.ydbio.2019.10.022_bib53","doi-asserted-by":"crossref","first-page":"3611","DOI":"10.1242\/dev.025361","article-title":"Frs2alpha-deficiency in cardiac progenitors disrupts a subset of FGF signals required for outflow tract morphogenesis","volume":"135","author":"Zhang","year":"2008","journal-title":"Development"},{"key":"10.1016\/j.ydbio.2019.10.022_bib54","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1210\/me.2007-0140","article-title":"Fibroblast growth factor receptor 1 (FGFR1) tyrosine phosphorylation regulates binding of FGFR substrate 2 alpha (FRS2alpha) but not FRS2 to the receptor","volume":"22","author":"Zhang","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"10.1016\/j.ydbio.2019.10.022_bib55","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/cr.2008.328","article-title":"Non-Smad pathways in TGF-beta signaling","volume":"19","author":"Zhang","year":"2009","journal-title":"Cell Res."}],"container-title":["Developmental Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012160619303902?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0012160619303902?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T04:42:20Z","timestamp":1757911340000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0012160619303902"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2]]},"references-count":55,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,2]]}},"alternative-id":["S0012160619303902"],"URL":"https:\/\/doi.org\/10.1016\/j.ydbio.2019.10.022","relation":{},"ISSN":["0012-1606"],"issn-type":[{"type":"print","value":"0012-1606"}],"subject":[],"published":{"date-parts":[[2020,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"FRS2\u03b1-dependent cell fate transition during endocardial cushion morphogenesis","name":"articletitle","label":"Article Title"},{"value":"Developmental Biology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ydbio.2019.10.022","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Published by Elsevier Inc.","name":"copyright","label":"Copyright"}]}}