{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:25:31Z","timestamp":1792794331771,"version":"4.5.0"},"reference-count":69,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Herman B Wells Center for Pediatric Research"},{"name":"Riley Children\u2019s Foundation, Division of Pediatric Cardiology","id":[{"id":"https:\/\/ror.org\/03sabpy05","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Carrolton Buehl McCulloch Chair of Pediatrics"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL134599-01"],"award-info":[{"award-number":["P01 HL134599-01"]}],"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 HL145060-01"],"award-info":[{"award-number":["R01 HL145060-01"]}],"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 HL122123-04"],"award-info":[{"award-number":["R01 HL122123-04"]}],"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 HL120920-04"],"award-info":[{"award-number":["R01 HL120920-04"]}],"id":[{"id":"10.13039\/100000002","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:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To examine the role of the basic Helix-loop-Helix (bHLH) transcription factor HAND1 in embryonic and adult myocardium.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Hand1 is expressed within the cardiomyocytes of the left ventricle (LV) and myocardial cuff between embryonic days (E) 9.5\u201313.5. Hand gene dosage plays an important role in ventricular morphology and the contribution of Hand1 to congenital heart defects requires further interrogation. Conditional ablation of Hand1 was carried out using either Nkx2.5 knockin Cre (Nkx2.5Cre) or \u03b1-myosin heavy chain Cre (\u03b1Mhc-Cre) driver. Interrogation of transcriptome data via ingenuity pathway analysis reveals several gene regulatory pathways disrupted including translation and cardiac hypertrophy-related pathways. Embryo and adult hearts were subjected to histological, functional, and molecular analyses. Myocardial deletion of Hand1 results in morphological defects that include cardiac conduction system defects, survivable interventricular septal defects, and abnormal LV papillary muscles (PMs). Resulting Hand1 conditional mutants are born at Mendelian frequencies; but the morphological alterations acquired during cardiac development result in, the mice developing diastolic heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, these data reveal that HAND1 contributes to the morphogenic patterning and maturation of cardiomyocytes during embryogenesis and although survivable, indicates a role for Hand1 within the developing conduction system and PM development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvz182","type":"journal-article","created":{"date-parts":[[2019,7,5]],"date-time":"2019-07-05T15:09:06Z","timestamp":1562339346000},"page":"605-618","source":"Crossref","is-referenced-by-count":39,"title":["HAND1 loss-of-function within the embryonic myocardium reveals survivable congenital cardiac defects and adult heart failure"],"prefix":"10.1093","volume":"116","author":[{"given":"Beth A","family":"Firulli","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. 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Walnut St, Indianapolis, IN 46202-5225, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-6187","authenticated-orcid":false,"given":"Loren J","family":"Field","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St, Indianapolis, IN 46202-5225, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St, Indianapolis, IN 46202-5225, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5538-9605","authenticated-orcid":false,"given":"Weinian","family":"Shou","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. Walnut St, Indianapolis, IN 46202-5225, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6232-3628","authenticated-orcid":false,"given":"Ronald Mark","family":"Payne","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, 1044 W. 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