{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:46:21Z","timestamp":1789145181490,"version":"build-2803163510"},"reference-count":64,"publisher":"The Company of Biologists","issue":"19","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"crossref","award":["2P01HL134599"],"award-info":[{"award-number":["2P01HL134599"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008113","name":"Indiana University-Purdue University Indianapolis","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008113","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The bHLH transcription factors HAND1 and HAND2 are expressed in partially overlapping patterns during development. Studies have established evidence for significant functional redundancy between HAND1 and HAND2. To test redundancy fully, we engineered a Hand1 allele in which we directly replaced the Hand1 exons and intron with those of Hand2. The results show that 2% of Hand1Hand2\/Hand2 mice are viable and fertile. The remaining Hand1Hand2\/Hand2 embryos exhibit neonatal lethality due to omphalocele accompanied by ventricular septal defects and conduction anomalies. Omphalocele can occur due to altered gut rotation. Our transcriptomic expression analysis reveals that established gene expression patterns associated with normal gut rotation are compromised. Interrogation of cardiac function in surviving Hand1Hand2\/Hand2 mice reveals QRS abnormalities and cardiac morphogenic defects. These data support previous findings that HAND factors exhibit extensive functional overlap but also reveals that HAND1 protein has unique functions within the Hand1 expression domain and is required for normal embryonic development.<\/jats:p>","DOI":"10.1242\/dev.204963","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T13:01:07Z","timestamp":1758114067000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>Hand1<\/i>\n                    gene replacement with\n                    <i>Hand2<\/i>\n                    reveals overlap in function with unique occurrence of omphalocele and heart defects"],"prefix":"10.1242","volume":"152","author":[{"given":"Beth A.","family":"Firulli","sequence":"first","affiliation":[{"name":"Indiana University School of Medicine 1 Herman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics , , 1044 W. Walnut Street, Indianapolis, IN 46202-5225 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe A.","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine 1 Herman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics , , 1044 W. Walnut Street, Indianapolis, IN 46202-5225 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corrie","family":"de Gier-de Vries","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam 2 Department of Medical Biology , , 22660, 1100 DD Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram","family":"Podicheti","sequence":"additional","affiliation":[{"name":"Center for Genomics and Bioinformatics, Indiana University 3 , Bloomington, IN 47405 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas B.","family":"Rusch","sequence":"additional","affiliation":[{"name":"Center for Genomics and Bioinformatics, Indiana University 3 , Bloomington, IN 47405 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent M.","family":"Christoffels","sequence":"additional","affiliation":[{"name":"Academic Medical Center, University of Amsterdam 2 Department of Medical Biology , , 22660, 1100 DD Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Rubart-von der Lohe","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine 1 Herman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics , , 1044 W. Walnut Street, Indianapolis, IN 46202-5225 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6687-8949","authenticated-orcid":false,"given":"Anthony B.","family":"Firulli","sequence":"additional","affiliation":[{"name":"Indiana University School of Medicine 1 Herman B Wells Center for Pediatric Research Department of Pediatrics, Anatomy, Biochemistry, and Medical and Molecular Genetics , , 1044 W. Walnut Street, Indianapolis, IN 46202-5225 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"2025110408270216000_DEV204963C1","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.ydbio.2007.07.036","article-title":"Hand transcription factors cooperatively regulate development of the distal midline mesenchyme","volume":"310","author":"Barbosa","year":"2007","journal-title":"Dev. 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