Genes that Regulate Heart Development

调节心脏发育的基因

• 批准号: 7071810
• 负责人: ERIC N Olson
• 金额: $ 49.65万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7071810
• 关键词: amidohydrolases; biological signal transduction; cardiogenesis; developmental genetics; embryonic stem cell; genetic mapping; genetic regulatory element; genetically modified animals; laboratory mouse; mammalian embryology; microarray technology; myocardium; myogenesis; smooth muscle; tissue /cell culture; transcription factor; yeast two hybrid system

Elucidation of the mechanisms that specify cardiac muscle cell fate is one of the central issues in cardiovascular biology. We have recently discovered a novel transcription factor, named myocardin, which is expressed specifically in embryonic and adult cardiac and smooth muscle cells. Myocardin belongs to the SAP domain family of nuclear proteins and activates cardiac and smooth muscle genes by associating with serum response factor (SRF), a widely expressed MADS box transcription factor that regulates differentiation and proliferation of muscle cells. Expression of a dominant negative mutant of myocardin in Xenopus embryos interferes with heart formation and myocardial cell differentiation, and ectopic expression of myocardin induces cardiac and smooth muscle gene expression. The overall goal of this project is to define the mechanisms whereby myocardin regulates cardiac and smooth muscle development and to identify regulatory factors and signaling systems that govern myocardin activity and expression. These studies will provide fundamental insights into the mechanisms involved in cardiovascular development and disease, and should advance strategies for regeneration and repair of the cardiovascular system.

阐明指定心肌细胞命运的机制是中心问题之一 心血管生物学。我们最近发现了一种新的转录因子，称为心肌蛋白，该因子专门在胚胎和成人心脏和平滑肌细胞中表达。心肌蛋白属于核蛋白的SAP结构域家族，并通过与血清反应因子（SRF）相关联，激活心脏和平滑肌基因，这是一种广泛表达的MADS转录因子，可调节肌肉细胞的分化和增殖。爪蟾胚胎中心肌蛋白的显性阴性突变体的表达会干扰心脏形成和心肌细胞分化，而肌心蛋白的异位表达会诱导心脏和平滑肌基因表达。该项目的总体目标是定义心肌素来调节心脏和平滑肌发育的机制以及 确定控制心肌素活性和表达的调节因素和信号系统。这些研究将提供对心血管发育和疾病所涉及的机制的基本见解，并应促进心血管系统再生和修复策略。