Fine-scale Spatiotemporal Mapping of Cellular Regulatory Networks Directing Heart Development

项目摘要 先天性心脏病是新生儿中最常见的先天畸形，占三分之一 在所有主要的先天畸形中。尽管最近的先天性心脏病基因研究强调了 心脏转录和染色质调节因子在心脏发育中的关键作用，我们对 这些发育调节因子如何相互作用以创建动态的基因调控网络 心脏发育仍有待充分阐明。因此，我们建议定义和分析心血管疾病 发育调节器及其基因调控网络，指导着大量 心血管细胞类型创造了哺乳动物的心脏。为了实现这一目标，一个多学科的实验 并将应用计算系统生物学方法：(1)阐明基因调控网络 建立发育中的哺乳动物心脏的心脏细胞层次结构，(2)研究 小鼠胚胎发育和心脏发育过程中心脏细胞层级的时空组织 形态发生和(3)从功能上研究不同的心血管发育来源如何创造特定的 心血管血统对心脏发育有贡献。

Project Summary Congenital Heart Disease is the most common congenital anomaly in newborn babies, accounting for one third of all major congenital anomalies. Despite recent congenital heart disease genetic studies highlighting the critical role of cardiac transcriptional and chromatin regulators during heart development, our understanding of how these developmental regulators interact to create the dynamic gene regulatory networks that mediate heart development remains to be fully elucidated. Thus, we propose to define and assay the cardiovascular developmental regulators and their gene regulatory networks that direct the development of the vast array of cardiovascular cell types creating the mammalian heart. To achieve this goal, a multi-disciplinary experimental and computational systems biology approach will be implemented to: (1) elucidate gene regulatory networks that establish the cardiogenic cellular hierarchy of the developing mammalian heart, (2) investigate the spatiotemporal organization of the cardiogenic cellular hierarchy during mouse embryogenesis and heart morphogenesis and (3) functionally examine how distinct cardiovascular developmental sources create specific cardiovascular lineages contributing to the developing heart.