The chromatin regulator Ankrd11 controls cardiac neural crest cell-mediated outflow tract remodeling and heart function

Yana Kibalnyk, Elia Afanasiev, Ronan M. N. Noble, Adrianne E. S. Watson, Irina Poverennaya, Nicole L. Dittmann, Maria Alexiou, Kara Goodkey, Amanda A. Greenwell, John R. Ussher, Igor Adameyko, James Massey, Daniel Graf, Stephane L. Bourque, Jo Anne Stratton and Anastassia Voronova ()
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Yana Kibalnyk: University of Alberta
Elia Afanasiev: McGill University
Ronan M. N. Noble: University of Alberta
Adrianne E. S. Watson: University of Alberta
Irina Poverennaya: Medical University of Vienna
Nicole L. Dittmann: University of Alberta
Maria Alexiou: University of Alberta
Kara Goodkey: University of Alberta
Amanda A. Greenwell: University of Alberta
John R. Ussher: University of Alberta
Igor Adameyko: Medical University of Vienna
James Massey: Vizgen Inc.
Daniel Graf: University of Alberta
Stephane L. Bourque: University of Alberta
Jo Anne Stratton: McGill University
Anastassia Voronova: University of Alberta

Nature Communications, 2024, vol. 15, issue 1, 1-20

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-48955-1

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