{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:47:44Z","timestamp":1782949664845,"version":"3.54.5"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>The collagen- and calcium-binding EGF-like domains 1 (CCBE1) is a secreted protein extensively described as indispensable for lymphangiogenesis during development enhancing VEGF-C signaling. In human patients, mutations in <jats:italic>CCBE1<\/jats:italic> have been found to cause Hennekam syndrome, an inherited disease characterized by malformation of the lymphatic system that presents a wide variety of symptoms such as primary lymphedema, lymphangiectasia, and heart defects. Importantly, over the last decade, an essential role for CCBE1 during heart development is being uncovered. In mice, <jats:italic>Ccbe1<\/jats:italic> expression was initially detected in distinct cardiac progenitors such as first and second heart field, and the proepicardium. More recently, <jats:italic>Ccbe1<\/jats:italic> expression was identified in the epicardium and sinus venosus (SV) myocardium at E11.5\u2013E13.5, the stage when SV endocardium\u2013derived (VEGF-C dependent) coronary vessels start to form. Concordantly, CCBE1 is required for the correct formation of the coronary vessels and the coronary artery stem in the mouse. Additionally, <jats:italic>Ccbe1<\/jats:italic> was found to be enriched in mouse embryonic stem cells (ESC) and revealed as a new essential gene for the differentiation of ESC-derived early cardiac precursor cell lineages. Here, we bring an up-to-date review on the role of CCBE1 in cardiac development, function, and human disease implications. Finally, we envisage the potential of this molecule\u2019s functions from a regenerative medicine perspective, particularly novel therapeutic strategies for heart disease.<\/jats:p>","DOI":"10.3389\/fgene.2022.836694","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T07:52:08Z","timestamp":1644393128000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["CCBE1 in Cardiac Development and Disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Fernando","family":"Bonet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"In\u00e1cio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Bover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina B.","family":"A\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A.","family":"Belo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1038\/ng.484","article-title":"Mutations in CCBE1 Cause Generalized Lymph Vessel Dysplasia in Humans","volume":"41","author":"Alders","year":"2009","journal-title":"Nat. Genet."},{"key":"B2","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1159\/000342486","article-title":"Evaluation of Clinical Manifestations in Patients with Severe Lymphedema with and without CCBE1 Mutations","volume":"4","author":"Alders","year":"2012","journal-title":"Mol. Syndromol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1161\/CIRCULATIONAHA.106.618082","article-title":"Coronary Artery Anomalies: An Entity in Search of an Identity","volume":"115","author":"Angelini","year":"2007","journal-title":"Circulation"},{"key":"B4","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1038\/sj.bjc.6605429","article-title":"Collagen and Calcium-Binding EGF Domains 1 Is Frequently Inactivated in Ovarian Cancer by Aberrant Promoter Hypermethylation and Modulates Cell Migration and Survival","volume":"102","author":"Barton","year":"2010","journal-title":"Br. J. Cancer"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1161\/CIRCULATIONAHA.105.592345","article-title":"Adult Congenital Heart Disease","volume":"115","author":"Bashore","year":"2007","journal-title":"Circulation"},{"key":"B6","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/j.gep.2011.07.002","article-title":"Identification of Differentially Expressed Genes in the Heart Precursor Cells of the Chick Embryo","volume":"11","author":"Bento","year":"2011","journal-title":"Gene Expr. Patterns"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1002\/dvdy.24670","article-title":"CCBE1 Is Required for Coronary Vessel Development and Proper Coronary Artery Stem Formation in the Mouse Heart","volume":"247","author":"Bonet","year":"2018","journal-title":"Dev. Dyn."},{"key":"B8","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1161\/CIRCRESAHA.111.250738","article-title":"CCBE1 Is Essential for Mammalian Lymphatic Vascular Development and Enhances the Lymphangiogenic Effect of Vascular Endothelial Growth Factor-C In Vivo","volume":"109","author":"Bos","year":"2011","journal-title":"Circ. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"e0205108","DOI":"10.1371\/journal.pone.0205108","article-title":"Loss of Ccbe1 Affects Cardiac-Specification and Proliferation in Differentiating Mouse Embryonic Stem Cells","volume":"13","author":"Bover","year":"2018","journal-title":"PLoS ONE"},{"key":"B10","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1021\/bp.13910.1002\/btpr.139","article-title":"Engineering the Embryoid Body Microenvironment to Direct Embryonic Stem Cell Differentiation","volume":"25","author":"Bratt-leal","year":"2009","journal-title":"Biotechnol. Prog."},{"key":"B11","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nrg1710","article-title":"Building the Mammalian Heart from Two Sources of Myocardial Cells","volume":"6","author":"Buckingham","year":"2005","journal-title":"Nat. Rev. Genet."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2167","DOI":"10.1172\/JCI83967","article-title":"Proteolytic Activation Defines Distinct Lymphangiogenic Mechanisms for VEGFC and VEGFD","volume":"126","author":"Bui","year":"2016","journal-title":"J. Clin. Invest."},{"key":"B13","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1073\/pnas.1509834113","article-title":"Extracardiac Septum Transversum\/proepicardial Endothelial Cells Pattern Embryonic Coronary Arterio-Venous Connections","volume":"113","author":"Cano","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4899","DOI":"10.1172\/JCI77483","article-title":"VEGF-C and Aortic Cardiomyocytes Guide Coronary Artery Stem Development","volume":"124","author":"Chen","year":"","journal-title":"J. Clin. Invest."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4500","DOI":"10.1242\/dev.113639","article-title":"The Sinus Venosus Contributes to Coronary Vasculature through VEGFC-Stimulated Angiogenesis","volume":"141","author":"Chen","year":"","journal-title":"Development"},{"key":"B16","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/s00439-009-0766-y","article-title":"Linkage and Sequence Analysis Indicate that CCBE1 Is Mutated in Recessively Inherited Generalised Lymphatic Dysplasia","volume":"127","author":"Connell","year":"2010","journal-title":"Hum. Genet."},{"key":"B17","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1111\/j.1399-0004.2011.01731.x","article-title":"CCBE1 Mutations Can Cause a Mild, Atypical Form of Generalized Lymphatic Dysplasia but Are Not a Common Cause of Non-immune Hydrops Fetalis","volume":"81","author":"Connell","year":"2012","journal-title":"Clin. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1046\/j.1432-0436.2001.680404.x","article-title":"Embryonic Stem Cell Differentiation: The Role of Extracellular Factors","volume":"68","author":"Czyz","year":"2001","journal-title":"Differentiation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1006\/dbio.1997.8801","article-title":"Common Epicardial Origin of Coronary Vascular Smooth Muscle, Perivascular Fibroblasts, and Intermyocardial Fibroblasts in the Avian Heart","volume":"193","author":"Dettman","year":"1998","journal-title":"Develop. Biol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2245","DOI":"10.1101\/gad.12.15.2245","article-title":"The Regulation of E2F by pRB-Family Proteins","volume":"12","author":"Dyson","year":"1998","journal-title":"Genes Dev."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1387\/ijdb.113394jf","article-title":"Ccbe1 Expression marks the Cardiac and Lymphatic Progenitor Lineages during Early Stages of Mouse Development","volume":"55","author":"Facucho-Oliveira","year":"2011","journal-title":"Int. J. Dev. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/376066a0","article-title":"Role of the Flt-1 Receptor Tyrosine Kinase in Regulating the Assembly of Vascular Endothelium","volume":"376","author":"Fong","year":"1995","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3015","DOI":"10.1242\/dev.126.13.3015","article-title":"Increased Hemangioblast Commitment, Not Vascular Disorganization, Is the Primary Defect in Flt-1 Knock-Out Mice","volume":"126","author":"Fong","year":"1999","journal-title":"Development"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e115481","DOI":"10.1371\/journal.pone.0115481","article-title":"Expression and Function of Ccbe1 in the Chick Early Cardiogenic Regions Are Required for Correct Heart Development","volume":"9","author":"Furtado","year":"2014","journal-title":"PLoS ONE"},{"key":"B25","doi-asserted-by":"publisher","first-page":"e61856","DOI":"10.1371\/journal.pone.0061856","article-title":"Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation","volume":"8","author":"Goh","year":"2013","journal-title":"PLoS One"},{"key":"B26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.26355\/eurrev-201801-1410410.26355\/eurrev_201801_14104","article-title":"The Regulatory Role of SLP-2 and Mechanism on CCBE1 Gene Expression in Rectal Carcinoma and Adjacent Lymphatic Tube Tissues","volume":"22","author":"Guo","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/emboj.2012.340","article-title":"A Novel Multistep Mechanism for Initial Lymphangiogenesis in Mouse Embryos Based on Ultramicroscopy","volume":"32","author":"H\u00e4gerling","year":"2013","journal-title":"Embo J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"3793","DOI":"10.1182\/blood.v96.12.379310.1182\/blood.v96.12.3793.h8003793_3793_3800","article-title":"VEGF-C Signaling Pathways through VEGFR-2 and VEGFR-3 in Vasculoangiogenesis and Hematopoiesis","volume":"96","author":"Hamada","year":"2000","journal-title":"Blood"},{"key":"B29","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/s0959-437x(98)80058-0","article-title":"Regulation of Cell Proliferation by the E2F Transcription Factors","volume":"8","author":"Helin","year":"1998","journal-title":"Curr. Opin. Genet. Develop."},{"key":"B30","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1002\/ajmg.1320340429","article-title":"Autosomal Recessive Intestinal Lymphangiectasia and Lymphedema, with Facial Anomalies and Mental Retardation","volume":"34","author":"Hennekam","year":"1989","journal-title":"Am. J. Med. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.jbiosc.2012.10.004","article-title":"Heart Extracellular Matrix Supports Cardiomyocyte Differentiation of Mouse Embryonic Stem Cells","volume":"115","author":"Higuchi","year":"2013","journal-title":"J. Biosci. Bioeng."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1242\/dev.02294","article-title":"PAR3 Is Essential for Cyst-Mediated Epicardial Development by Establishing Apical Cortical Domains","volume":"133","author":"Hirose","year":"2006","journal-title":"Development"},{"key":"B33","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/ng.321","article-title":"Ccbe1 Is Required for Embryonic Lymphangiogenesis and Venous Sprouting","volume":"41","author":"Hogan","year":"2009","journal-title":"Nat. Genet."},{"key":"B34","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.devcel.2008.12.007","article-title":"Cardiac Fibroblasts Regulate Myocardial Proliferation through \u03b21 Integrin Signaling","volume":"16","author":"Ieda","year":"2009","journal-title":"Develop. Cell"},{"key":"B35","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1172\/JCI44244","article-title":"Cardiac Neural Crest Orchestrates Remodeling and Functional Maturation of Mouse Semilunar Valves","volume":"121","author":"Jain","year":"2011","journal-title":"J. Clin. Invest."},{"key":"B36","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1084\/jem.20132308","article-title":"Lymphatic Function Is Required Prenatally for Lung Inflation at Birth","volume":"211","author":"Jakus","year":"2014","journal-title":"J. Exp. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1962","DOI":"10.1161\/CIRCULATIONAHA.113.002779","article-title":"CCBE1Enhances Lymphangiogenesis via A Disintegrin and Metalloprotease with Thrombospondin Motifs-3-Mediated Vascular Endothelial Growth Factor-C Activation","volume":"129","author":"Jeltsch","year":"2014","journal-title":"Circulation"},{"key":"B38","doi-asserted-by":"publisher","first-page":"e44478","DOI":"10.7554\/eLife.44478","article-title":"KLK3\/PSA and Cathepsin D Activate VEGF-C and VEGF-D","volume":"17","author":"Jha","year":"2019","journal-title":"Elife"},{"key":"B39","doi-asserted-by":"publisher","first-page":"4916","DOI":"10.1038\/s41598-017-04982-1","article-title":"Efficient Activation of the Lymphangiogenic Growth Factor VEGF-C Requires the C-Terminal Domain of VEGF-C and the N-Terminal Domain of CCBE1","volume":"7","author":"Jha","year":"2017","journal-title":"Sci. Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"3898","DOI":"10.1093\/emboj\/16.13.3898","article-title":"Proteolytic Processing Regulates Receptor Specificity and Activity of VEGF-C","volume":"16","author":"Joukov","year":"1997","journal-title":"Embo J."},{"key":"B41","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ni1013","article-title":"Vascular Endothelial Growth Factor C Is Required for Sprouting of the First Lymphatic Vessels from Embryonic Veins","volume":"5","author":"Karkkainen","year":"2004","journal-title":"Nat. Immunol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1016\/j.devcel.2012.01.012","article-title":"Distinct Compartments of the Proepicardial Organ Give Rise to Coronary Vascular Endothelial Cells","volume":"22","author":"Katz","year":"2012","journal-title":"Develop. Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/B978-0-12-387786-4.00002-6","article-title":"The Second Heart Field","volume":"100","author":"Kelly","year":"2012","journal-title":"Curr. Top. Dev. Biol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1242\/dev.100495","article-title":"Ccbe1 Regulates Vegfc-Mediated Induction of Vegfr3 Signaling during Embryonic Lymphangiogenesis","volume":"141","author":"Le Guen","year":"2014","journal-title":"Development"},{"key":"B45","first-page":"125","article-title":"Mesenchymal Derivatives of the Neural Crest: Analysis of Chimaeric Quail and Chick Embryos","volume":"34","author":"Le Li\u00e8vre","year":"1975","journal-title":"J. Embryol. Exp. Morphol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1093\/ije\/dyz009","article-title":"Global Birth Prevalence of Congenital Heart Defects 1970-2017: Updated Systematic Review and Meta-Analysis of 260 Studies","volume":"48","author":"Liu","year":"2019","journal-title":"Int. J. Epidemiol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1159\/000047867","article-title":"The Origin, Formation and Developmental Significance of the Epicardium: A Review","volume":"169","author":"M\u00e4nner","year":"2001","journal-title":"Cells Tissues Organs"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/bjc.2017.105","article-title":"Targeting of CCBE1 by miR-330-3p in Human Breast Cancer Promotes Metastasis","volume":"116","author":"Mesci","year":"2017","journal-title":"Br. J. Cancer"},{"key":"B49","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1006\/dbio.1996.0068","article-title":"Pericardial Mesoderm Generates a Population of Coronary Smooth Muscle Cells Migrating into the Heart along with Ingrowth of the Epicardial Organ","volume":"174","author":"Mikawa","year":"1996","journal-title":"Develop. Biol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1006\/dbio.2001.0409","article-title":"The Outflow Tract of the Heart Is Recruited from a Novel Heart-Forming Field","volume":"238","author":"Mjaatvedt","year":"2001","journal-title":"Develop. Biol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1152\/physrev.00006.2003","article-title":"Cardiac Chamber Formation: Development, Genes, and Evolution","volume":"83","author":"Moorman","year":"2003","journal-title":"Physiol. Rev."},{"key":"B52","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1136\/heart.89.7.806","article-title":"Development of the Heart: (1) Formation of the Cardiac chambers and Arterial Trunks","volume":"89","author":"Moorman","year":"2003","journal-title":"Heart"},{"key":"B53","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1161\/01.RES.73.3.559","article-title":"Development of the Cardiac Coronary Vascular Endothelium, Studied with Antiendothelial Antibodies, in Chicken-Quail Chimeras","volume":"73","author":"Poelmann","year":"1993","journal-title":"Circ. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nature08873","article-title":"Coronary Arteries Form by Developmental Reprogramming of Venous Cells","volume":"464","author":"Red-Horse","year":"2010","journal-title":"Nature"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1660","DOI":"10.1161\/CIRCRESAHA.116.304949","article-title":"Functional Dissection of the CCBE1 Protein","volume":"116","author":"Roukens","year":"2015","journal-title":"Circ. Res."},{"key":"B56","doi-asserted-by":"publisher","first-page":"e75770","DOI":"10.1371\/journal.pone.0075770","article-title":"CCBE1 Mutation in Two Siblings, One Manifesting Lymphedema-Cholestasis Syndrome, and the Other, Fetal Hydrops","volume":"8","author":"Shah","year":"2013","journal-title":"PLoS ONE"},{"key":"B57","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/j.devcel.2017.08.008","article-title":"Alternative Progenitor Cells Compensate to Rebuild the Coronary Vasculature in Elabela- and Apj-Deficient Hearts","volume":"42","author":"Sharma","year":"2017","journal-title":"Develop. Cell"},{"key":"B58","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.jbiotec.2018.08.015","article-title":"Full-length Human CCBE1 Production and Purification: Leveraging Bioprocess Development for High Quality Glycosylation Attributes and Functionality","volume":"285","author":"Silva","year":"2018","journal-title":"J. Biotechnol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"2327","DOI":"10.7150\/thno.39740","article-title":"CCBE1 Promotes Tumor Lymphangiogenesis and Is Negatively Regulated by TGF\u03b2 Signaling in Colorectal Cancer","volume":"10","author":"Song","year":"2020","journal-title":"Theranostics"},{"key":"B60","doi-asserted-by":"publisher","first-page":"4484","DOI":"10.1242\/dev.078790","article-title":"A Fast and Sensitive Alternative for \u03b2-galactosidase Detection in Mouse Embryos","volume":"139","author":"Sundararajan","year":"2012","journal-title":"Development"},{"key":"B61","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1038\/nature07083","article-title":"Blocking VEGFR-3 Suppresses Angiogenic Sprouting and Vascular Network Formation","volume":"454","author":"Tammela","year":"2008","journal-title":"Nature"},{"key":"B62","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1002\/stem.1453","article-title":"Defined Extracellular Matrix Components Are Necessary for Definitive Endoderm Induction","volume":"31","author":"Taylor-Weiner","year":"2013","journal-title":"Stem Cells"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/srep31071","article-title":"CCBE1 Promotes GIST Development through Enhancing Angiogenesis and Mediating Resistance to Imatinib","volume":"6","author":"Tian","year":"2016","journal-title":"Sci. Rep."},{"key":"B64","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s10456-005-9014-9","article-title":"Formation of the Coronary Vasculature during Development","volume":"8","author":"Tomanek","year":"2005","journal-title":"Angiogenesis"},{"key":"B65","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1002\/ajmg.10707","article-title":"Lymphedema-lymphangiectasia-mental Retardation (Hennekam) Syndrome: a Review","volume":"112","author":"Van Balkom","year":"2002","journal-title":"Am. J. Med. Genet."},{"key":"B66","doi-asserted-by":"publisher","first-page":"e254","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart Disease and Stroke Statistics-2021 Update","volume":"23143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"B67","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1002\/(sici)1097-0177(199703)208:3<338:aid-aja5>3.0.co;2-j","article-title":"The Development of the Coronary Vessels and Their Differentiation into Arteries and Veins in the Embryonic Quail Heart","volume":"208","author":"Vrancken Peeters","year":"1997","journal-title":"Dev. Dyn."},{"key":"B68","doi-asserted-by":"publisher","first-page":"3179","DOI":"10.1242\/dev.128.16.3179","article-title":"Conotruncal Myocardium Arises from a Secondary Heart Field","volume":"128","author":"Waldo","year":"2001","journal-title":"Development"},{"key":"B69","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/aja.1001880202","article-title":"Origin of the Proximal Coronary Artery Stems and a Review of Ventricular Vascularization in the Chick Embryo","volume":"188","author":"Waldo","year":"1990","journal-title":"Am. J. Anat."},{"key":"B70","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1006\/dbio.1998.8860","article-title":"Cardiac Neural Crest Cells Provide New Insight into Septation of the Cardiac Outflow Tract: Aortic Sac to Ventricular Septal Closure","volume":"196","author":"Waldo","year":"1998","journal-title":"Develop. Biol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"3871","DOI":"10.1038\/emboj.2012.231","article-title":"E2F7 and E2F8 Promote Angiogenesis through Transcriptional Activation of VEGFA in Cooperation with HIF1","volume":"31","author":"Weijts","year":"2012","journal-title":"EMBO J."},{"key":"B72","doi-asserted-by":"publisher","first-page":"e73693","DOI":"10.1371\/journal.pone.0073693","article-title":"Atypical E2fs Control Lymphangiogenesis through Transcriptional Regulation of Ccbe1 and Flt4","volume":"8","author":"Weijts","year":"2013","journal-title":"PLoS ONE"},{"key":"B73","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ydbio.2010.12.025","article-title":"Cell Proliferation in the Absence of E2F1-3","volume":"351","author":"Wenzel","year":"2011","journal-title":"Develop. Biol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/j.cell.2012.10.023","article-title":"Endocardial Cells Form the Coronary Arteries by Angiogenesis through Myocardial-Endocardial VEGF Signaling","volume":"151","author":"Wu","year":"2012","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1002\/elps.200700093","article-title":"Scanning Copy Number and Gene Expression on the 18q21-Qter Chromosomal Region by the Systematic Multiplex PCR and Reverse Transcription-PCR Methods","volume":"28","author":"Yamamoto","year":"2007","journal-title":"Electrophoresis"},{"key":"B76","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1161\/0110.1161\/01.res.0000136815.73623.be","article-title":"Right Ventricular Myocardium Derives from the Anterior Heart Field","volume":"95","author":"Zaffran","year":"2004","journal-title":"Circ. Res."},{"key":"B77","doi-asserted-by":"publisher","first-page":"3335","DOI":"10.1242\/dev.037903","article-title":"Spatial and Temporal Regulation of Coronary Vessel Formation by Calcineurin-NFAT Signaling","volume":"136","author":"Zeini","year":"2009","journal-title":"Development"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/1471-2121-14-5","article-title":"Collagen\/\u03b21 Integrin Interaction Is Required for Embryoid Body Formation during Cardiogenesis from Murine Induced Pluripotent Stem Cells","volume":"14","author":"Zeng","year":"2013","journal-title":"BMC Cell Biol"},{"key":"B79","first-page":"1214","article-title":"Expression of SLP-2 Gene and CCBE1 Are Associated with Prognosis of Rectal Cancer","volume":"21","author":"Zhang","year":"2017","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"6581","DOI":"10.2147\/CMAR.S181770","article-title":"The Clinical Significance of CCBE1 Expression in Human Colorectal Cancer","volume":"10","author":"Zhao","year":"2018","journal-title":"Cancer Manage. Res."},{"key":"B81","doi-asserted-by":"publisher","first-page":"e65755","DOI":"10.1371\/journal.pone.0065755","article-title":"Contrasting Roles of E2F2 and E2F3 in Cardiac Neovascularization","volume":"8","author":"Zhou","year":"2013","journal-title":"PLoS ONE"},{"key":"B82","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2021\/9951405","article-title":"miR-942-5p Inhibits Proliferation, Metastasis, and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting CCBE1","volume":"2021","author":"Zhou","year":"2021","journal-title":"Biomed. Res. Int."},{"key":"B83","doi-asserted-by":"publisher","first-page":"3228","DOI":"10.1182\/blood-2012-10-462689","article-title":"The Secreted Lymphangiogenic Factor CCBE1 Is Essential for Fetal Liver Erythropoiesis","volume":"121","author":"Zou","year":"2013","journal-title":"Blood"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.836694\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T07:52:13Z","timestamp":1644393133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2022.836694\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,9]]},"references-count":83,"alternative-id":["10.3389\/fgene.2022.836694"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2022.836694","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,9]]},"article-number":"836694"}}