BVES AND INTRACARDIAC ARTERY DEVELOPMENT

心脏的发育涉及多种细胞类型的产生和相互作用，以形成一个功能器官。心肌细胞、心内膜、成纤维细胞、心外膜、血管内皮和平滑肌细胞是构成心脏的主要细胞类型。心外膜前器官是许多这些细胞的来源。它是一种短暂的胚胎结构，其后代形成心外膜和心内动脉，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至关重要。为了确定控制心脏器官发生的分子机制，我们已经分离出在形态发生过程中表达的新的心脏特异性信息。其中一种信息Bves在大多数（如果不是全部的话）心外膜外器官细胞、迁移心外膜细胞、脱层自由迁移间质细胞和血管平滑肌细胞中表达。此外，Bves的亚细胞定位随着该细胞系的分化发生了巨大的变化。我们的目标是确定Bves在这一复杂过程中的正常表达模式（目的1），Bves功能如何被已知的心脏形态发生突变所改变（目的2），以及Bves功能的丧失如何潜在地改变形态发生（目的3）。综上所述，这些目标将确定Bves的功能，其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.