Ankrd11, a chromatin regulator and a KBG syndrome risk gene, is a critical regulator of cardiac neural crest cell biology and heart development

Ankrd11, a chromatin regulator and a KBG syndrome risk gene, is a critical regulator of cardiac neural crest cell biology and heart development | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Ankrd11, a chromatin regulator and a KBG syndrome risk gene, is a critical regulator of cardiac neural crest cell biology and heart development Yana Kibalnyk, Ronan Noble, Maria Alexiou, Irina Poverennaya, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2605378/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 01 Jul, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a risk gene for KBG syndrome, a rare developmental disorder characterized by multiple organ abnormalities, including cardiac defects. However, the role of ANKRD11 in heart development is unknown. The neural crest plays a leading role in embryonic heart development, and its dysfunction is implicated in many congenital heart defects. Here, we demonstrate that conditional knockout of Ankrd11 in the murine embryonic neural crest leads to a severe congenital cardiac defect termed persistent truncus arteriosus (PTA), ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization and failure to initiate outflow tract septation. Finally, conditional knockout of Ankrd11 in the neural crest leads to impaired Sema3C (Semaphorin 3C) expression, and reduced mTOR (mammalian target of rapamycin) and BMP (Bone Morphogenetic Protein) signaling in the cardiac neural crest cells within the outflow tract. This study identifies Ankrd11 as a novel regulator of neural crest-mediated heart development and function and suggests a mechanism for aberrant heart development in KBG syndrome patients. Biological sciences/Developmental biology/Embryogenesis/Cell lineage Biological sciences/Cell biology/Mechanisms of disease CHD PTA VSD OFT cardiovascular neurodevelopmental disorder epigenetic ANCO1 histone acetylation Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementalvideo1Ankrd11ctrl.mp4 Supplemental Video 1 Supplementalvideo2Ankrd11ncko.mp4 Supplemental Video 2 Cite Share Download PDF Status: Published Journal Publication published 01 Jul, 2024 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2605378","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":178505396,"identity":"e93d9c01-e7d0-413c-b346-9df6eab24f04","order_by":0,"name":"Yana Kibalnyk","email":"","orcid":"","institution":"University of Alberta","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yana","middleName":"","lastName":"Kibalnyk","suffix":""},{"id":178505397,"identity":"7f6b192a-8a58-4144-8566-7aa706408e6e","order_by":1,"name":"Ronan Noble","email":"","orcid":"","institution":"University of 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