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- Title
The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function.
- Authors
Kibalnyk, Yana; Afanasiev, Elia; Noble, Ronan M. N.; Watson, Adrianne E. S.; Poverennaya, Irina; Dittmann, Nicole L.; Alexiou, Maria; Goodkey, Kara; Greenwell, Amanda A.; Ussher, John R.; Adameyko, Igor; Massey, James; Graf, Daniel; Bourque, Stephane L.; Stratton, Jo Anne; Voronova, Anastassia
- Abstract
ANKRD11 (Ankyrin Repeat Domain 11) is a chromatin regulator and a causative 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 that 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. Lastly, 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 regulator of neural crest-mediated heart development and function. Ankrd11 is a chromatin regulator that is strongly associated with KBG syndrome, a rare disorder that includes heart defects. Here they show that loss of Ankrd11 from neural crest dysregulates cardiac neural crest cell organization and crucial signaling pathways, leading to failed heart outflow tract septation and severe cardiac defects.
- Subjects
NEURAL crest; CHROMATIN; CONGENITAL heart disease; HEART development; EMBRYOLOGY; BRUGADA syndrome
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-48955-1