{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:46:00Z","timestamp":1790952360538,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T00:00:00Z","timestamp":1698192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-CE12-0002"],"award-info":[{"award-number":["ANR-17-CE12-0002"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cornelia de Lange Syndrome (CdLS) patients, who frequently carry a mutation in NIPBL, present an increased incidence of outflow tract (OFT)-related congenital heart defects (CHDs). Nipbl+\/- mice recapitulate a number of phenotypic traits of CdLS patients, including a small body size and cardiac defects, but no study has specifically focused on the valves. Here, we show that adult Nipbl+\/- mice present aortic valve thickening, a condition that has been associated with stenosis. During development, we observed that OFT septation and neural crest cell condensation was delayed in Nipbl+\/- embryos. However, we did not observe defects in the deployment of the main lineages contributing to the semilunar valves. Indeed, endocardial endothelial-to-mesenchymal transition (EndMT), analysed via outflow tract explants, and neural crest migration, analysed via genetic lineage tracing, did not significantly differ in Nipbl+\/- mice and their wild-type littermates. Our study provides the first direct evidence for valve formation defects in Nipbl+\/- mice and points to specific developmental defects as an origin for valve disease in patients.<\/jats:p>","DOI":"10.3390\/ijms242115564","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T06:19:58Z","timestamp":1698214798000},"page":"15564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nipbl Haploinsufficiency Leads to Delayed Outflow Tract Septation and Aortic Valve Thickening"],"prefix":"10.3390","volume":"24","author":[{"given":"Fanny","family":"Boulet","sequence":"first","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle, University of Montpellier, Centre National de la Recherche Scientifique, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, 34094 Montpellier, France"},{"name":"Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-7114","authenticated-orcid":false,"given":"Gaelle","family":"Odelin","sequence":"additional","affiliation":[{"name":"Aix Marseille University, INSERM, MMG, 13005 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0162-2795","authenticated-orcid":false,"given":"Alenca","family":"Harrington","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle, University of Montpellier, Centre National de la Recherche Scientifique, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Moore-Morris","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9nomique Fonctionnelle, University of Montpellier, Centre National de la Recherche Scientifique, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, 34094 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/S0140-6736(06)69208-8","article-title":"Burden of valvular heart diseases: A population-based study","volume":"368","author":"Nkomo","year":"2006","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/eurheartj\/ehx391","article-title":"2017 ESC\/EACTS Guidelines for the management of valvular heart disease","volume":"38","author":"Baumgartner","year":"2017","journal-title":"Eur. 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