{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:49:56Z","timestamp":1787021396628,"version":"build-2736575974"},"reference-count":96,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":344,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL112893"],"award-info":[{"award-number":["R01 HL112893"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL137766"],"award-info":[{"award-number":["R01 HL137766"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL141186"],"award-info":[{"award-number":["R01 HL141186"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["18POST34050034"],"award-info":[{"award-number":["18POST34050034"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Vertebrate heart development requires the integration of temporally distinct differentiating progenitors. However, few signals are understood that restrict the size of the later-differentiating outflow tract (OFT). We show that improper specification and proliferation of second heart field (SHF) progenitors in zebrafish lazarus (lzr) mutants, which lack the transcription factor Pbx4, produces enlarged hearts owing to an increase in ventricular and smooth muscle cells. Specifically, Pbx4 initially promotes the partitioning of the SHF into anterior progenitors, which contribute to the OFT, and adjacent endothelial cell progenitors, which contribute to posterior pharyngeal arches. Subsequently, Pbx4 limits SHF progenitor (SHFP) proliferation. Single cell RNA sequencing of nkx2.5+ cells revealed previously unappreciated distinct differentiation states and progenitor subpopulations that normally reside within the SHF and arterial pole of the heart. Specifically, the transcriptional profiles of Pbx4-deficient nkx2.5+ SHFPs are less distinct and display characteristics of normally discrete proliferative progenitor and anterior, differentiated cardiomyocyte populations. Therefore, our data indicate that the generation of proper OFT size and arch arteries requires Pbx-dependent stratification of unique differentiation states to facilitate both homeotic-like transformations and limit progenitor production within the SHF.<\/jats:p>","DOI":"10.1242\/dev.185652","type":"journal-article","created":{"date-parts":[[2020,2,24]],"date-time":"2020-02-24T18:39:22Z","timestamp":1582569562000},"source":"Crossref","is-referenced-by-count":17,"title":["Pbx4 limits heart size and fosters arch artery formation by partitioning second heart field progenitors and restricting proliferation"],"prefix":"10.1242","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2341-5746","authenticated-orcid":false,"given":"Andrew","family":"Holowiecki","sequence":"first","affiliation":[{"name":"Molecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Research Foundation 1 , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Linstrum","sequence":"additional","affiliation":[{"name":"Molecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Research Foundation 1 , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"University of Cincinnati College of Medicine 2 Molecular Genetics Graduate Program , , Cincinnati, OH 45267 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7061-9875","authenticated-orcid":false,"given":"Padmapriyadarshini","family":"Ravisankar","sequence":"additional","affiliation":[{"name":"Molecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Research Foundation 1 , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9314-5759","authenticated-orcid":false,"given":"Kashish","family":"Chetal","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Research Foundation 3 Bioinformatics Division , , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9689-2469","authenticated-orcid":false,"given":"Nathan","family":"Salomonis","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Research Foundation 3 Bioinformatics Division , , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"University of Cincinnati College of Medicine 4 Department of Pediatrics , , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-487X","authenticated-orcid":false,"given":"Joshua S.","family":"Waxman","sequence":"additional","affiliation":[{"name":"Molecular Cardiovascular Biology Division and Heart Institute, Cincinnati Children's Research Foundation 1 , Cincinnati, OH 45229 ,","place":["USA"]},{"name":"University of Cincinnati College of Medicine 4 Department of Pediatrics , , Cincinnati, OH 45229 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,3,2]]},"reference":[{"key":"2026041419033813100_DEV185652C1","doi-asserted-by":"publisher","first-page":"4603","DOI":"10.1038\/s41467-018-07054-8","article-title":"Loss of embryonic neural crest derived cardiomyocytes causes adult onset hypertrophic cardiomyopathy in zebrafish","volume":"9","author":"Abdul-Wajid","year":"2018","journal-title":"Nat. Commun."},{"key":"2026041419033813100_DEV185652C2","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/j.celrep.2017.07.002","article-title":"TGF-\u03b2 signaling is necessary and sufficient for pharyngeal arch artery angioblast formation","volume":"20","author":"Abrial","year":"2017","journal-title":"Cell Rep."},{"key":"2026041419033813100_DEV185652C3","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.ydbio.2008.03.022","article-title":"Loss of unc45a precipitates arteriovenous shunting in the aortic arches","volume":"318","author":"Anderson","year":"2008","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C4","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1101\/gad.1207204","article-title":"Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry","volume":"18","author":"Arenkiel","year":"2004","journal-title":"Genes Dev."},{"key":"2026041419033813100_DEV185652C5","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.ejmg.2012.02.002","article-title":"Non-synonymous variants in pre-B cell leukemia homeobox (PBX) genes are associated with congenital heart defects","volume":"55","author":"Arrington","year":"2012","journal-title":"Eur. J. Med. Genet."},{"key":"2026041419033813100_DEV185652C6","doi-asserted-by":"publisher","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":"2026041419033813100_DEV185652C7","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1016\/j.ydbio.2011.02.029","article-title":"Hox genes define distinct progenitor sub-domains within the second heart field","volume":"353","author":"Bertrand","year":"2011","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C8","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/j.ydbio.2008.01.038","article-title":"Complex cell rearrangements during intersegmental vessel sprouting and vessel fusion in the zebrafish embryo","volume":"316","author":"Blum","year":"2008","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C9","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.ydbio.2015.06.002","article-title":"Two developmentally distinct populations of neural crest cells contribute to the zebrafish heart","volume":"404","author":"Cavanaugh","year":"2015","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C10","doi-asserted-by":"publisher","first-page":"3577","DOI":"10.1242\/dev.022350","article-title":"Pbx1 functions in distinct regulatory networks to pattern the great arteries and cardiac outflow tract","volume":"135","author":"Chang","year":"2008","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C11","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1242\/dev.129.3.585","article-title":"Meis family proteins are required for hindbrain development in the zebrafish","volume":"129","author":"Choe","year":"2002","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C12","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1002\/ajmg.a.33375","article-title":"Further evidence for the possible role of MEIS2 in the development of cleft palate and cardiac septum","volume":"152A","author":"Crowley","year":"2010","journal-title":"Am. J. Med. Genet. A"},{"key":"2026041419033813100_DEV185652C13","doi-asserted-by":"publisher","first-page":"e1003689","DOI":"10.1371\/journal.pgen.1003689","article-title":"Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid","volume":"9","author":"D'Aniello","year":"2013","journal-title":"PLoS Genet."},{"key":"2026041419033813100_DEV185652C14","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1242\/dev.030924","article-title":"Distinct phases of cardiomyocyte differentiation regulate growth of the zebrafish heart","volume":"136","author":"de Pater","year":"2009","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C15","doi-asserted-by":"publisher","first-page":"e138","DOI":"10.1093\/nar\/gkz789","article-title":"cellHarmony: cell-level matching and holistic comparison of single-cell transcriptomes","volume":"47","author":"DePasquale","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2026041419033813100_DEV185652C16","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1016\/j.ydbio.2011.10.032","article-title":"Distinct phases of Wnt\/beta-catenin signaling direct cardiomyocyte formation in zebrafish","volume":"361","author":"Dohn","year":"2012","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C17","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.celrep.2015.08.065","article-title":"Sequential binding of MEIS1 and NKX2-5 on the Popdc2 gene: a mechanism for spatiotemporal regulation of enhancers during cardiogenesis","volume":"13","author":"Dupays","year":"2015","journal-title":"Cell Rep."},{"key":"2026041419033813100_DEV185652C18","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1016\/j.ydbio.2006.08.022","article-title":"Pbx proteins cooperate with engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries","volume":"301","author":"Erickson","year":"2007","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C19","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1242\/dev.127.1.155","article-title":"Segmental expression of Hoxb2 in r4 requires two separate sites that integrate cooperative interactions between Prep1, Pbx and Hox proteins","volume":"127","author":"Ferretti","year":"2000","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C20","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1242\/dev.136606","article-title":"Multicolor mapping of the cardiomyocyte proliferation dynamics that construct the atrium","volume":"143","author":"Foglia","year":"2016","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C21","doi-asserted-by":"publisher","first-page":"6147","DOI":"10.1128\/MCB.20.16.6147-6158.2000","article-title":"Functional collaboration between different cyclin-dependent kinase inhibitors suppresses tumor growth with distinct tissue specificity","volume":"20","author":"Franklin","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"2026041419033813100_DEV185652C22","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1146\/annurev.pharmtox.41.1.507","article-title":"Lysophospholipid receptors","volume":"41","author":"Fukushima","year":"2001","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"2026041419033813100_DEV185652C23","doi-asserted-by":"publisher","first-page":"dev167510","DOI":"10.1242\/dev.167510","article-title":"Hey2 regulates the size of the cardiac progenitor pool during vertebrate heart development","volume":"145","author":"Gibb","year":"2018","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C24","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1002\/dvg.22833","article-title":"Two new targeted alleles for the comprehensive analysis of Meis1 functions in the mouse","volume":"52","author":"Gonz\u00e1lez-L\u00e1zaro","year":"2014","journal-title":"Genesis"},{"key":"2026041419033813100_DEV185652C25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ctdb.2016.11.010","article-title":"Modeling syndromic congenital heart defects in zebrafish","volume":"124","author":"Grant","year":"2017","journal-title":"Curr. Top. Dev. Biol."},{"key":"2026041419033813100_DEV185652C26","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1242\/dev.088351","article-title":"Zebrafish second heart field development relies on progenitor specification in anterior lateral plate mesoderm and nkx2.5 function","volume":"140","author":"Guner-Ataman","year":"2013","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C27","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.1016\/j.celrep.2018.06.117","article-title":"Failed progenitor specification underlies the cardiopharyngeal phenotypes in a zebrafish model of 22q11.2 deletion syndrome","volume":"24","author":"Guner-Ataman","year":"2018","journal-title":"Cell Rep."},{"key":"2026041419033813100_DEV185652C28","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.exphem.2018.09.004","article-title":"The human cell atlas bone marrow single-cell interactive web portal","volume":"68","author":"Hay","year":"2018","journal-title":"Exp. Hematol."},{"key":"2026041419033813100_DEV185652C29","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.ydbio.2012.06.019","article-title":"Zebrafish Mef2ca and Mef2cb are essential for both first and second heart field cardiomyocyte differentiation","volume":"369","author":"Hinits","year":"2012","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C30","doi-asserted-by":"publisher","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":"2026041419033813100_DEV185652C31","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.ahj.2003.05.003","article-title":"Prevalence of congenital heart disease","volume":"147","author":"Hoffman","year":"2004","journal-title":"Am. Heart J."},{"key":"2026041419033813100_DEV185652C32","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1002\/dvdy.10356","article-title":"Germ-line transmission of a myocardium-specific GFP transgene reveals critical regulatory elements in the cardiac myosin light chain 2 promoter of zebrafish","volume":"228","author":"Huang","year":"2003","journal-title":"Dev. Dyn."},{"key":"2026041419033813100_DEV185652C33","doi-asserted-by":"publisher","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":"2026041419033813100_DEV185652C34","doi-asserted-by":"publisher","first-page":"1673","DOI":"10.1093\/jnci\/djs373","article-title":"Dual suppression of the cyclin-dependent kinase inhibitors CDKN2C and CDKN1A in human melanoma","volume":"104","author":"Jalili","year":"2012","journal-title":"J. Natl. Cancer Inst."},{"key":"2026041419033813100_DEV185652C35","doi-asserted-by":"publisher","first-page":"14008","DOI":"10.1073\/pnas.0702240104","article-title":"Vertebrate heart growth is regulated by functional antagonism between Gridlock and Gata5","volume":"104","author":"Jia","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041419033813100_DEV185652C36","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3390\/jdb3040093","article-title":"Pbx4 is required for the temporal onset of zebrafish myocardial differentiation","volume":"3","author":"Kao","year":"2015","journal-title":"J. Dev. Biol."},{"key":"2026041419033813100_DEV185652C37","doi-asserted-by":"publisher","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":"2026041419033813100_DEV185652C38","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1006\/dbio.2001.0201","article-title":"Specification and morphogenesis of the zebrafish larval head skeleton","volume":"233","author":"Kimmel","year":"2001","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C39","doi-asserted-by":"publisher","first-page":"6611","DOI":"10.18632\/oncotarget.2844","article-title":"Loss of p21Cip1\/CDKN1A renders cancer cells susceptible to Polo-like kinase 1 inhibition","volume":"6","author":"Kreis","year":"2015","journal-title":"Oncotarget"},{"key":"2026041419033813100_DEV185652C40","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.ydbio.2011.03.028","article-title":"Mef2cb regulates late myocardial cell addition from a second heart field-like population of progenitors in zebrafish","volume":"354","author":"Lazic","year":"2011","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C41","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.ydbio.2008.01.037","article-title":"Identification of downstream genetic pathways of Tbx1 in the second heart field","volume":"316","author":"Liao","year":"2008","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C42","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1016\/j.cell.2016.01.004","article-title":"Complex interdependence regulates heterotypic transcription factor distribution and coordinates cardiogenesis","volume":"164","author":"Luna-Zurita","year":"2016","journal-title":"Cell"},{"key":"2026041419033813100_DEV185652C43","doi-asserted-by":"publisher","first-page":"2138","DOI":"10.1016\/j.cub.2003.11.055","article-title":"heart of glass regulates the concentric growth of the heart in zebrafish","volume":"13","author":"Mably","year":"2003","journal-title":"Curr. Biol."},{"key":"2026041419033813100_DEV185652C44","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/S1388-1981(02)00341-4","article-title":"Sphingosine kinase, sphingosine-1-phosphate, and apoptosis","volume":"1585","author":"Maceyka","year":"2002","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"2026041419033813100_DEV185652C45","doi-asserted-by":"publisher","first-page":"16621","DOI":"10.1523\/JNEUROSCI.4769-10.2010","article-title":"DeltaA\/DeltaD regulate multiple and temporally distinct phases of notch signaling during dopaminergic neurogenesis in zebrafish","volume":"30","author":"Mahler","year":"2010","journal-title":"J. Neurosci."},{"key":"2026041419033813100_DEV185652C46","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1038\/nature12054","article-title":"Meis1 regulates postnatal cardiomyocyte cell cycle arrest","volume":"497","author":"Mahmoud","year":"2013","journal-title":"Nature"},{"key":"2026041419033813100_DEV185652C47","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1242\/dev.003905","article-title":"Pbx homeodomain proteins direct Myod activity to promote fast-muscle differentiation","volume":"134","author":"Maves","year":"2007","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C48","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.ydbio.2009.07.004","article-title":"Pbx acts with Hand2 in early myocardial differentiation","volume":"333","author":"Maves","year":"2009","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C49","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1242\/dev.129.10.2339","article-title":"Knockdown of duplicated zebrafish hoxb1 genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention","volume":"129","author":"McClintock","year":"2002","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C50","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.matbio.2006.09.011","article-title":"Differential expression of two tropoelastin genes in zebrafish","volume":"26","author":"Miao","year":"2007","journal-title":"Matrix Biol."},{"key":"2026041419033813100_DEV185652C51","doi-asserted-by":"publisher","first-page":"10397","DOI":"10.1038\/ncomms10397","article-title":"Evolution of the fish heart by sub\/neofunctionalization of an elastin gene","volume":"7","author":"Moriyama","year":"2016","journal-title":"Nat. Commun."},{"key":"2026041419033813100_DEV185652C52","doi-asserted-by":"publisher","first-page":"e1001181","DOI":"10.1371\/journal.pbio.1001181","article-title":"Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of cornelia de lange syndrome","volume":"9","author":"Muto","year":"2011","journal-title":"PLoS Biol."},{"key":"2026041419033813100_DEV185652C53","doi-asserted-by":"publisher","first-page":"2099","DOI":"10.1016\/j.cub.2015.06.076","article-title":"Origin, specification, and plasticity of the great vessels of the heart","volume":"25","author":"Nagelberg","year":"2015","journal-title":"Curr. Biol."},{"key":"2026041419033813100_DEV185652C54","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/wdev.98","article-title":"Cardiac outflow tract anomalies","volume":"2","author":"Neeb","year":"2013","journal-title":"Wiley Interdiscip. Rev. Dev. Biol."},{"key":"2026041419033813100_DEV185652C55","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1002\/dvdy.23928","article-title":"Tbx1 is required for second heart field proliferation in zebrafish","volume":"242","author":"Nevis","year":"2013","journal-title":"Dev. Dyn."},{"key":"2026041419033813100_DEV185652C56","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/nature19348","article-title":"Single-cell analysis of mixed-lineage states leading to a binary cell fate choice","volume":"537","author":"Olsson","year":"2016","journal-title":"Nature"},{"key":"2026041419033813100_DEV185652C57","doi-asserted-by":"publisher","first-page":"1087","DOI":"10.1093\/nar\/21.5.1087","article-title":"Cloning of the zebrafish krox-20 gene (krx-20) and its expression during hindbrain development","volume":"21","author":"Oxtoby","year":"1993","journal-title":"Nucleic Acids Res."},{"key":"2026041419033813100_DEV185652C58","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1038\/ncb2862","article-title":"Heart field origin of great vessel precursors relies on nkx2.5-mediated vasculogenesis","volume":"15","author":"Paffett-Lugassy","year":"2013","journal-title":"Nat. Cell Biol."},{"key":"2026041419033813100_DEV185652C59","doi-asserted-by":"publisher","first-page":"4616","DOI":"10.1242\/dev.153411","article-title":"Unique developmental trajectories and genetic regulation of ventricular and outflow tract progenitors in the zebrafish second heart field","volume":"144","author":"Paffett-Lugassy","year":"2017","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C60","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/ng.517","article-title":"Genome-wide association study of PR interval","volume":"42","author":"Pfeufer","year":"2010","journal-title":"Nat. Genet."},{"key":"2026041419033813100_DEV185652C61","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1006\/dbio.2000.9842","article-title":"The endoderm plays an important role in patterning the segmented pharyngeal region in zebrafish (Danio rerio)","volume":"225","author":"Piotrowski","year":"2000","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C62","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/S1097-2765(00)00027-7","article-title":"lazarus is a novel pbx gene that globally mediates hox gene function in zebrafish","volume":"6","author":"P\u00f6pperl","year":"2000","journal-title":"Mol. Cell"},{"key":"2026041419033813100_DEV185652C63","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ydbio.2010.08.036","article-title":"Cranial vasculature in zebrafish forms by angioblast cluster-derived angiogenesis","volume":"348","author":"Proulx","year":"2010","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C64","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nmeth.4150","article-title":"Single-cell mRNA quantification and differential analysis with Census","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"2026041419033813100_DEV185652C65","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1038\/nmeth.4402","article-title":"Reversed graph embedding resolves complex single-cell trajectories","volume":"14","author":"Qiu","year":"2017","journal-title":"Nat. Methods"},{"key":"2026041419033813100_DEV185652C66","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1161\/CIRCRESAHA.115.305020","article-title":"Tbx1 coordinates addition of posterior second heart field progenitor cells to the arterial and venous poles of the heart","volume":"115","author":"Rana","year":"2014","journal-title":"Circ. Res."},{"key":"2026041419033813100_DEV185652C67","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":"2026041419033813100_DEV185652C68","doi-asserted-by":"publisher","first-page":"4614","DOI":"10.1074\/jbc.M115.683912","article-title":"High-throughput functional genomics identifies regulators of primary human beta cell proliferation","volume":"291","author":"Robitaille","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2026041419033813100_DEV185652C69","doi-asserted-by":"publisher","first-page":"e78","DOI":"10.1371\/journal.pgen.0030078","article-title":"p53 Activation by Knockdown Technologies","volume":"3","author":"Robu","year":"2007","journal-title":"PLoS Genet."},{"key":"2026041419033813100_DEV185652C70","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/jdb4020014","article-title":"Hox genes in cardiovascular development and diseases","volume":"4","author":"Roux","year":"2016","journal-title":"J. Dev. Biol."},{"key":"2026041419033813100_DEV185652C71","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.ydbio.2015.08.015","article-title":"Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development","volume":"406","author":"Roux","year":"2015","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C72","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1089\/zeb.2016.1413","article-title":"itFISH: enhanced staining by iterative fluorescent in situ hybridization","volume":"14","author":"Row","year":"2017","journal-title":"Zebrafish"},{"key":"2026041419033813100_DEV185652C73","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12859-017-1934-z","article-title":"ImageJ2: ImageJ for the next generation of scientific image data","volume":"18","author":"Rueden","year":"2017","journal-title":"BMC Bioinformatics"},{"key":"2026041419033813100_DEV185652C74","doi-asserted-by":"publisher","first-page":"2913","DOI":"10.1073\/pnas.0712344105","article-title":"Retinoic acid deficiency alters second heart field formation","volume":"105","author":"Ryckebusch","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2026041419033813100_DEV185652C75","doi-asserted-by":"publisher","first-page":"e2000504","DOI":"10.1371\/journal.pbio.2000504","article-title":"Cyp26 enzymes facilitate second heart field progenitor addition and maintenance of ventricular integrity","volume":"14","author":"Rydeen","year":"2016","journal-title":"PLoS Biol."},{"key":"2026041419033813100_DEV185652C76","doi-asserted-by":"publisher","first-page":"e53877","DOI":"10.3791\/53877","article-title":"Isolation and characterization of single cells from zebrafish embryos","author":"Samsa","year":"2016","journal-title":"J. Vis. Exp."},{"key":"2026041419033813100_DEV185652C77","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"2026041419033813100_DEV185652C78","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1242\/dev.106336","article-title":"Hand2 elevates cardiomyocyte production during zebrafish heart development and regeneration","volume":"141","author":"Schindler","year":"2014","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C79","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1038\/nprot.2008.73","article-title":"Analyzing real-time PCR data by the comparative CT method","volume":"3","author":"Schmittgen","year":"2008","journal-title":"Nat. Protoc."},{"key":"2026041419033813100_DEV185652C80","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1002\/dvdy.21570","article-title":"Retinoic acid controls heart anteroposterior patterning by down-regulating Isl1 through the Fgf8 pathway","volume":"237","author":"Sirbu","year":"2008","journal-title":"Dev. Dyn."},{"key":"2026041419033813100_DEV185652C81","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.ydbio.2011.07.022","article-title":"Restraint of Fgf8 signaling by retinoic acid signaling is required for proper heart and forelimb formation","volume":"358","author":"Sorrell","year":"2011","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C82","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/bs.mcb.2016.03.022","article-title":"Cellular dissection of zebrafish hematopoiesis","volume":"133","author":"Stachura","year":"2016","journal-title":"Methods Cell Biol."},{"key":"2026041419033813100_DEV185652C83","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1161\/CIRCRESAHA.108.175489","article-title":"Pbx\/Meis deficiencies demonstrate multigenetic origins of congenital heart disease","volume":"103","author":"Stankunas","year":"2008","journal-title":"Circ. Res."},{"key":"2026041419033813100_DEV185652C84","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1146\/annurev-genet-110711-155646","article-title":"Uncovering the molecular and cellular mechanisms of heart development using the zebrafish","volume":"46","author":"Staudt","year":"2012","journal-title":"Annu. Rev. Genet."},{"key":"2026041419033813100_DEV185652C85","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1242\/dev.125.6.1025","article-title":"Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning","volume":"125","author":"Studer","year":"1998","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C86","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat. Biotechnol."},{"key":"2026041419033813100_DEV185652C87","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.cell.2012.07.035","article-title":"Dynamic and coordinated epigenetic regulation of developmental transitions in the cardiac lineage","volume":"151","author":"Wamstad","year":"2017","journal-title":"Cell"},{"key":"2026041419033813100_DEV185652C88","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.ydbio.2016.12.010","article-title":"Endothelium in the pharyngeal arches 3, 4 and 6 is derived from the second heart field","volume":"421","author":"Wang","year":"2017","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C89","doi-asserted-by":"publisher","first-page":"4139","DOI":"10.3410\/f.1004495.19155","article-title":"Zebrafish Meis functions to stabilize Pbx proteins and regulate hindbrain patterning","volume":"128","author":"Waskiewicz","year":"2001","journal-title":"Development"},{"key":"2026041419033813100_DEV185652C90","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1016\/S1534-5807(02)00319-2","article-title":"Eliminating zebrafish pbx proteins reveals a hindbrain ground state","volume":"3","author":"Waskiewicz","year":"2002","journal-title":"Dev. Cell"},{"key":"2026041419033813100_DEV185652C91","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1016\/j.devcel.2008.09.009","article-title":"Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict heart field potential in zebrafish","volume":"15","author":"Waxman","year":"2008","journal-title":"Dev. Cell"},{"key":"2026041419033813100_DEV185652C92","volume-title":"The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio)","author":"Westerfield","year":"2000"},{"key":"2026041419033813100_DEV185652C93","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1006\/dbio.1999.9406","article-title":"Restricted expression of cardiac myosin genes reveals regulated aspects of heart tube assembly in zebrafish","volume":"214","author":"Yelon","year":"1999","journal-title":"Dev. Biol."},{"key":"2026041419033813100_DEV185652C94","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.celrep.2014.04.013","article-title":"Cadm4 restricts the production of cardiac outflow tract progenitor cells","volume":"7","author":"Zeng","year":"2014","journal-title":"Cell Rep."},{"key":"2026041419033813100_DEV185652C95","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/nature12322","article-title":"In vivo cardiac reprogramming contributes to zebrafish heart regeneration","volume":"498","author":"Zhang","year":"2013","journal-title":"Nature"},{"key":"2026041419033813100_DEV185652C96","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/nature10094","article-title":"Latent TGF-beta binding protein 3 identifies a second heart field in zebrafish","volume":"474","author":"Zhou","year":"2011","journal-title":"Nature"}],"container-title":["Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1242\/dev.185652","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.185652\/3481364\/dev185652.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.185652\/2064548\/dev_185652v1.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/journals.biologists.com\/dev\/article-pdf\/doi\/10.1242\/dev.185652\/3481364\/dev185652.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:03:45Z","timestamp":1776207825000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/dev\/article\/147\/5\/dev185652\/223132\/Pbx4-limits-heart-size-and-fosters-arch-artery"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,1]]},"references-count":96,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,3,1]]}},"URL":"https:\/\/doi.org\/10.1242\/dev.185652","relation":{},"ISSN":["1477-9129","0950-1991"],"issn-type":[{"value":"1477-9129","type":"electronic"},{"value":"0950-1991","type":"print"}],"subject":[],"published":{"date-parts":[[2020,3,1]]},"article-number":"dev185652"}}