PDF(Pubmed)
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.
摘要：
ANKRD11（Ankyrin重复结构域11）是一种染色质调节因子和KBG综合征的致病基因，一种罕见的以多器官异常为特征的发育障碍，包括心脏缺陷.然而,ANKRD11在心脏发育中的作用尚不清楚.神经嵴在胚胎心脏发育中起主导作用，它的功能障碍与先天性心脏缺陷有关。我们证明了鼠胚胎神经cast中Ankrd11的条件性敲除会导致持续的动脉干，心室扩张,和心室收缩力受损。我们进一步表明，这些缺陷是由于异常的心脏神经c细胞组织导致流出道分隔失败而发生的。最后,Ankrd11基因敲除导致各种转录因子的表达受损，染色质重塑和信号通路，包括mTOR,心脏神经c细胞中的BMP和TGF-β。在这项工作中,我们确定Ankrd11是神经c介导的心脏发育和功能的调节因子。
