BVES AND INTRACARDIAC ARTERY DEVELOPMENT

心脏发育涉及不同类型细胞的产生和相互作用，以形成一个功能器官。心肌细胞、心内膜、成纤维细胞、心外膜、血管内皮细胞和平滑肌细胞是构成心脏的主要细胞类型。心外膜器官是其中许多细胞的来源。它是一种暂时性的胚胎结构，其后代形成了心外膜和心内动脉，包括冠状动脉。因此，了解心外膜前器官及其后代的作用对于了解心脏发育是至关重要的。为了确定控制心脏器官发生的分子机制，我们分离了在形态发生过程中表达的新的心脏特异信息。一个这样的信号，BVES，表达在心外膜器官、移行的心外膜、剥离的自由移行间质和心脏血管平滑肌细胞中的大多数细胞中。此外，随着细胞系的分化，BVES的亚细胞定位发生了戏剧性的变化。我们的目标将确定在这个复杂的过程中BVES表达的正常模式(目标1)，BVES功能如何被心脏形态发生的已知突变改变(目标2)，以及BVES功能的丧失如何潜在地改变形态发生(目标3)。这些目标加在一起将决定BVES的功能(S)，它在心脏血管生成中的作用，以及对心内动脉发育的基本了解。

Heart development involves the generation and interaction of diverse cell types to form a functional organ. Myocytes, endocardium, fibroblasts, epicardium, vascular endothelium and smooth muscle cells are the primary cell types that comprise the heart. The proepicardial organ is the source of many of these cells. It is a transitory embryonic structure whose progeny form, amongst other structures, the epicardium and intracardiac arteries including the coronary arteries. Thus, an understanding of the role of the proepicardial organ and its progeny is essential for an understanding of heart development. In an effort to identify the molecular mechanisms governing heart organogenesis, we have isolated novel cardiac-specific messages expressed during morphogenesis. One such message, Bves, is expressed in most, if not all cells of the eproepicardial organ, migrating epicardial, delaminated freely migratory mesenchyme and cardiac vascular smooth muscle cells. In addition, the subcellular localization of Bves undergoes a dramatic change with differentiation of this cell lineage. Our aims will determine the normal pattern of Bves expression during this complex process (aim 1), how Bves function is altered by known mutations in cardiac morphogenesis (aim 2) and how loss of Bves function potentially alters morphogenesis (aim 3). Taken together these aims will determine the function(s) of Bves, its role in the generation of cardiac blood vessels and basic insight into intracardiac artery development.