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

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

PROVIDER: PRJNA1080268 | ENA |

REPOSITORIES: ENA

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

Project description: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 congenital heart defects. We demonstrate conditional knockout of Ankrd11 in the murine embryonic neural crest results in persistent truncus arteriosus, ventricular dilation, and impaired ventricular contractility. We further show these defects occur due to aberrant cardiac neural crest cell organization leading to outflow tract septation failure. Finally, knockout of Ankrd11 in the neural crest leads to impaired expression of various transcription factors, chromatin remodelers and signaling pathways, including mTOR, BMP and TGF-β in the cardiac neural crest cells. In this work, we identify Ankrd11 as a novel regulator of neural crest-mediated heart development and function.

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