{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:32:37Z","timestamp":1791045157069,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2011,11,11]]},"abstract":"<jats:sec>\n                    <jats:title>\n                      <jats:underline>Rationale:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>The development of the cardiac outflow tract (OFT) and great vessels is a complex process that involves coordinated regulation of multiple progenitor cell populations. Among these populations, neural crest cells make important contributions to OFT formation and aortic arch remodeling. Although numerous signaling pathways, including Notch, have been implicated in this process, the role of epigenetics in OFT development remains largely unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Objective:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>Because histone deacetylases (Hdacs) play important roles in the epigenetic regulation of mammalian development, we have investigated the function of Hdac3, a class I Hdac, during cardiac neural crest development in mouse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Methods and Results:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>\n                      Using 2 neural crest drivers,\n                      <jats:italic>Wnt1-Cre<\/jats:italic>\n                      and\n                      <jats:italic>\n                        Pax3\n                        <jats:sup>Cre<\/jats:sup>\n                      <\/jats:italic>\n                      , we show that loss of Hdac3 in neural crest results in perinatal lethality and cardiovascular abnormalities, including interrupted aortic arch type B, aortic arch hypoplasia, double-outlet right ventricle, and ventricular septal defect. Affected embryos are deficient in aortic arch artery smooth muscle during midgestation, despite intact neural crest cell migration and preserved development of other cardiac and truncal neural crest derivatives. The Hdac3-dependent block in smooth muscle differentiation is cell autonomous and is associated with downregulation of the Notch ligand Jagged1, a key driver of smooth muscle differentiation in the aortic arch arteries.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\n                      <jats:underline>Conclusions:<\/jats:underline>\n                    <\/jats:title>\n                    <jats:p>These results indicate that Hdac3 plays a critical and specific regulatory role in the neural crest-derived smooth muscle lineage and in formation of the OFT.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.111.255067","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T07:41:39Z","timestamp":1317368499000},"page":"1240-1249","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Histone Deacetylase 3 Regulates Smooth Muscle Differentiation in Neural Crest Cells and Development of the Cardiac Outflow Tract"],"prefix":"10.1161","volume":"109","author":[{"given":"Nikhil","family":"Singh","sequence":"first","affiliation":[{"name":"From the Department of Cell and Developmental Biology, the Cardiovascular Institute, the Institute for Regenerative Medicine (N.S., C.M.T., M.L., J.A.E.), the Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism (S.E.M., M.A.L.), Pereleman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and the Department of Medicine, University of Massachusetts Medical School, Worcester, MA (C.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chinmay M.","family":"Trivedi","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Developmental Biology, the Cardiovascular Institute, the Institute for Regenerative Medicine (N.S., C.M.T., M.L., J.A.E.), the Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism (S.E.M., M.A.L.), Pereleman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and the Department of Medicine, University of Massachusetts Medical School, Worcester, MA (C.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MinMin","family":"Lu","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Developmental Biology, the Cardiovascular Institute, the Institute for Regenerative Medicine (N.S., C.M.T., M.L., J.A.E.), the Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism (S.E.M., M.A.L.), Pereleman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and the Department of Medicine, University of Massachusetts Medical School, Worcester, MA (C.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon E.","family":"Mullican","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Developmental Biology, the Cardiovascular Institute, the Institute for Regenerative Medicine (N.S., C.M.T., M.L., J.A.E.), the Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism (S.E.M., M.A.L.), Pereleman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and the Department of Medicine, University of Massachusetts Medical School, Worcester, MA (C.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell A.","family":"Lazar","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Developmental Biology, the Cardiovascular Institute, the Institute for Regenerative Medicine (N.S., C.M.T., M.L., J.A.E.), the Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism (S.E.M., M.A.L.), Pereleman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and the Department of Medicine, University of Massachusetts Medical School, Worcester, MA (C.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Epstein","sequence":"additional","affiliation":[{"name":"From the Department of Cell and Developmental Biology, the Cardiovascular Institute, the Institute for Regenerative Medicine (N.S., C.M.T., M.L., J.A.E.), the Department of Medicine and the Institute for Diabetes, Obesity, and Metabolism (S.E.M., M.A.L.), Pereleman School of Medicine at the University of Pennsylvania, Philadelphia, PA; and the Department of Medicine, University of Massachusetts Medical School, Worcester, MA (C.M.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.05099.x"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0070-2153(10)90001-X"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.025437"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44630"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000155951.62152.2e"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2005.06.004"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30070"},{"key":"e_1_3_5_9_2","first-page":"1986","article-title":"Murine jagged1\/notch signaling in the second heart field orchestrates FGF8 expression and tissue-tissue interactions during outflow tract development","volume":"119","author":"High FA","year":"2009","unstructured":"High FA, Jain R, Stoller JZ, Antonucci NB, Lu MM, Loomes KM, Kaestner KH, Pear WS, Epstein JA. 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