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。主题是探索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。这项探索将由五个项目共有的实验胚胎学和分子生物学相结合来进行。房室管内皮细胞的上皮-间充质细胞转化是一个有趣的事件，它产生了瓣膜和膜性隔膜的最早的祖细胞。对这些细胞的研究将从三个层面探索细胞转化的调节。项目1将在三个水平上探索转录因子Slug和Mox-1作为细胞转化的中介。项目1将探索转录因子Slug和Mox-1作为细胞转化的中介，以响应TGFbeta和其他信号转导途径。项目2将探索钙粘附素和β-连环素在下调细胞、伴随细胞转化的细胞黏附中的作用。项目3的重点是透明质酸合成酶2(HAS2)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。这组研究人员感兴趣的还有心肌细胞的发育。项目4是对Nkx(Thinman)基因在心肌细胞前体对心脏表型的承诺中的作用的研究。项目5通过检查肌节的形成来研究心肌细胞的分化。为了了解收缩装置的组装规律，提出了对第三和第四丝系统的探索。这五个项目得到了行政和研究核心的支持。该研究核心将在反义寡核苷酸、病毒载体和整体原位杂交方面提供共同能力。行政核心将向所有项目提供支助，并利用外部审查委员会和定期安排的顾问提供审查和反馈。该项目旨在加强成员实验室之间的沟通，促进心脏发展的协同探索。通过该计划项目获得的信息将大大有助于我们对先天性心脏病的理解。

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.