Molecular networks of epicardial formation and function

摘要 先天性心脏病是西方世界的主要死亡原因，影响约1.3 百万美国人。心脏最初在脊椎动物体内形成为双层管，由内部的 心内膜和外心肌层。在开发的后期阶段，第三层被添加到 心脏来自心外膜，它由一个动态的前体结构形成，即心外膜器官 (PEO)，形成在横隔上，这是一个毗邻心脏的结构。作为胚胎 成熟后，PEO中的细胞迁移到心脏表面，最终形成几个基本细胞 成人心脏的类型包括心脏成纤维细胞和血管系统的平滑肌细胞。这个 这项提案的目的是利用我们一系列独特的技术、试剂和动物模型来 阐明血管形成和功能所需的分子和细胞途径 心外膜。为此，我们将提供一个研究心脏形成和止血的平台，以及 从而证明了对人类先天性心脏病的机械性洞察。

ABSTRACT Congenital heart disease is the leading cause of death in the western world affecting approximately 1.3 million Americans. The heart initially forms in vertebrates as a bilaminar tube comprised of an inner endocardium and outer myocardial layer. At later stages of development a third layer is added to the heart from the epicardium which forms from a dynamic precursor structure, the proepicardial organ (PEO) which forms on the septum transversum, a structure adjacent to the heart. As the embryo matures, cells from the PEO migrate onto the heart surface ultimately giving rise to several essential cell types in the adult heart including cardiac fibroblasts and the smooth muscle cells of the vasculature. The aim of this proposal will leverage our series of unique technologies, reagents, and animal models to elucidate the molecular and cellular pathways required for the formation and function of the epicardium. In doing so, we will provide a platform for studying heart formation and hemostasis, and thus proved mechanistic insight into human congenital heart disease.