COMMITMENT & DIFFERENTIATION OF CARDIAC CELL PHENOTYPES

提出了一个由5个项目和2个核心组成的计划项目。主题是胚胎心脏中两种细胞类型（内皮细胞和肌细胞）的承诺和分化的探索之一。这一探索将通过五个项目共同的实验胚胎学和分子生物学相结合来进行。一个关注的事件是房室管内皮细胞的上皮-间充质细胞转化，产生瓣膜和膜间隔的最早祖细胞。针对这些细胞的研究将在三个层面上探索细胞转化的调控。项目1将探讨转录因子Slug和Mox-1在三个水平上作为细胞转化的介质。项目1将探索转录因子Slug和Mox-1作为细胞转化的介导剂，响应TGF β和其他信号转导途径。项目2将探讨钙粘蛋白和β-连环蛋白在下调细胞中的作用，伴随细胞转化的细胞粘附。项目3的重点是透明质酸合酶2（Has 2）在心脏垫形成中的作用以及细胞转化和迁移对透明质酸的明显需求。这组研究人员还对心肌细胞的发育感兴趣。项目4是对Nkx（thinman）基因在心肌细胞前体向心脏表型定型中的作用的检查。 项目5的重点是通过检查肌节的形成来分化心肌细胞。探索第三和第四丝系统，以了解收缩装置组装的调节。这五个项目得到行政和研究核心的支持。该研究中心将提供反义寡核苷酸、病毒载体和整体原位杂交的共同能力。行政核心将为所有项目提供支助，并利用外部审查委员会和定期安排的咨询人提供审查和反馈。该计划旨在加强成员实验室之间的交流，促进心脏开发的协同探索。本计划所获得的资料将大大有助于我们对先天性心脏病的了解。

A Program Project consisting of 5 projects and 2 cores is proposed. The theme is one of an exploration of commitment and differentiation by two cell types in the embryonic heart, endothelia and myocytes. This exploration will be carried out by a combination of experimental embryology and molecular biology common to the five projects. One event of interest in the epithelial-mesenchymal cell transformation of endothelial cells in the atrioventricular canal that produces the earliest progenitors of the vales and membranous septa. Studies focused on these cells will explore the regulation of cell transformation at three levels. Project 1 will explore the transcription factors Slug and Mox-1 as mediators of cell transformation at three levels. Project 1 will explore the transcription factors Slug and Mox-1as mediators of cell transformation in response to TGFbeta and other signal transduction pathways. Project 2 will explore the role of cadherins and beta-catenin in the down-regulation of cell, cell adhesion that accompanies cell transformation. Project 3 is focused on the role of Hyaluronan Synthase 2 (Has2) in the formation of the cardiac cushions and the apparent requirement for hyaluronan for cell transformation and migration. Also of interest to this group of investigators is the development of cardiac myocytes. Project 4 is an examination of the role of Nkx (thinman) genes in commitment to the cardiac phenotype by myocyte precursors. Project 5 focuses on the differentiation of cardiac myocytes by examining the formation of the sarcomere. Exploration of the 3rd and 4th filament systems is proposed in order to understand the regulation of the assembly of the contractile apparatus. The five projects are supported by administrative and research cores. The research core will provide common capabilities in antisense oligonucleotides, viral vectors and whole mount in situ hybridization. The administrative core will provide support to all projects and utilize both an external review committee and regularly scheduled consultants to provide review and feedback. This program is designed to enhance communication between the member laboratories and promote the synergistic exploration of heart development. Information obtained by this Program Project will contribute significantly to our understanding of congenital heart disease.