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Here, we present data from four model systems that define roles for ETS factors in normal heart development and suggest how defects in these genes contribute to congenital heart disease. In frog, knockdown of\n                  <jats:italic>Ets1<\/jats:italic>\n                  in cardiac mesoderm led to a hypoplastic ventricle with impaired cardiac function and loss of trabecular myocardium. Grafting of wildtype cardiac mesodermal tissue restored the integrity of the ventricular endocardial layer and normal development. In zebrafish, KD of\n                  <jats:italic>ETS1<\/jats:italic>\n                  and two related\n                  <jats:italic>ETS<\/jats:italic>\n                  factor genes caused severely underdeveloped, poorly functioning ventricles with decreased numbers of endocardial cells that failed to contact the myocardium. Genetic ablation of the endocardium in mice also caused a hypoplastic ventricle with loss of the trabecular myocardium. In\n                  <jats:italic>Drosophila<\/jats:italic>\n                  , loss of the\n                  <jats:italic>ETS1<\/jats:italic>\n                  ortholog\n                  <jats:italic>pointed<\/jats:italic>\n                  (\n                  <jats:italic>pnt<\/jats:italic>\n                  ) affected specification of cardiac precursors and decreased Notch signaling, a pathway previously implicated in some forms of hypoplastic left heart syndrome (HLHS). We also demonstrated genetic interactions between\n                  <jats:italic>pnt<\/jats:italic>\n                  and\n                  <jats:italic>tinman<\/jats:italic>\n                  , the\n                  <jats:italic>NKX2.5<\/jats:italic>\n                  ortholog, associated with HLHS. Finally, our examination of the heart from a newborn with JS\/HLHS showed myofibrillar disarray and myocardial maturation defects. Furthermore, there was a reduction in the coronary vascular endothelium in the LV myocardium from the JS\/HLHS patient compared to an age-matched normal heart. Taken together, our studies demonstrate a critical and conserved role of ETS factors for cardiac endothelial function and in ventricular morphogenesis.\n                <\/jats:p>","DOI":"10.64898\/2026.09.08.26361286","type":"posted-content","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T03:50:18Z","timestamp":1789185018000},"source":"Crossref","is-referenced-by-count":0,"title":["Conserved roles of cardiac endothelial ETS factors in ventricular development and disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-5947","authenticated-orcid":false,"given":"Lu","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, UCSD School of Medicine, La Jolla, CA 92093, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7537-458X","authenticated-orcid":false,"given":"Analyne","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9635-3246","authenticated-orcid":false,"given":"Katya","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-5532","authenticated-orcid":false,"given":"Ingolf","family":"Reim","sequence":"additional","affiliation":[{"name":"Philipps-Universit\u00e4t Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4892-8161","authenticated-orcid":false,"given":"Matthias","family":"Blanc","sequence":"additional","affiliation":[{"name":"Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9918-9696","authenticated-orcid":false,"given":"K\u2019leigh","family":"Guillotte","sequence":"additional","affiliation":[{"name":"Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1625-6333","authenticated-orcid":false,"given":"Amelie","family":"M\u00fcck","sequence":"additional","affiliation":[{"name":"Philipps-Universit\u00e4t Marburg, 35043 Marburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0687-3463","authenticated-orcid":false,"given":"Elaina","family":"Bao","sequence":"additional","affiliation":[{"name":"Pathology, Rady Children\u2019s Hospital, San Diego, CA 92123, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1659-7381","authenticated-orcid":false,"given":"Zhi","family":"Ling","sequence":"additional","affiliation":[{"name":"Parker H. 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