University of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA Department of Biology, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
University of North Carolina McAllister Heart Institute, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA Department of Genetics, UNC-Chapel Hill, Chapel Hill, NC 27599-3280, USA.
Development. 2014 Aug;141(15):3040-9. doi: 10.1242/dev.106518. Epub 2014 Jul 3.
The identification and characterization of the cellular and molecular pathways involved in the differentiation and morphogenesis of specific cell types of the developing heart are crucial to understanding the process of cardiac development and the pathology associated with human congenital heart disease. Here, we show that the cardiac transcription factor CASTOR (CASZ1) directly interacts with congenital heart disease 5 protein (CHD5), which is also known as tryptophan-rich basic protein (WRB), a gene located on chromosome 21 in the proposed region responsible for congenital heart disease in individuals with Down's syndrome. We demonstrate that loss of CHD5 in Xenopus leads to compromised myocardial integrity, improper deposition of basement membrane, and a resultant failure of hearts to undergo cell movements associated with cardiac formation. We further report that CHD5 is essential for CASZ1 function and that the CHD5-CASZ1 interaction is necessary for cardiac morphogenesis. Collectively, these results establish a role for CHD5 and CASZ1 in the early stages of vertebrate cardiac development.
鉴定和描述参与发育中心脏特定细胞类型分化和形态发生的细胞和分子途径对于理解心脏发育过程和与人类先天性心脏病相关的病理学至关重要。在这里，我们表明心脏转录因子 CASTOR（CASZ1）与先天性心脏病 5 蛋白（CHD5）直接相互作用，CHD5 也称为富含色氨酸的碱性蛋白（WRB），是位于 21 号染色体上的一个基因，该基因位于唐氏综合征患者先天性心脏病的假定区域。我们证明，在非洲爪蟾中缺失 CHD5 会导致心肌完整性受损、基底膜沉积不当，以及心脏无法进行与心脏形成相关的细胞运动。我们进一步报告，CHD5 对于 CASZ1 功能是必需的，并且 CHD5-CASZ1 相互作用对于心脏形态发生是必要的。总的来说，这些结果确立了 CHD5 和 CASZ1 在脊椎动物心脏发育早期阶段的作用。
