CELL-CELL AND MATRIX ADHESION IN CARDIAC MORPHOGENESIS

1%的新生儿患有先天性心脏病，通常 在心脏的隔膜中。关于分子碱基，人们知之甚少 因为细胞过程驱动了一系列具有良好特征的 心脏发育过程中的形态变化。涉及的特定分子 细胞-底物黏附(SAM)和细胞-细胞黏附(CAMS)调节 在其他系统中的形态发生，并与发育相关 重要的主要过程，如细胞迁移、细胞分裂、 细胞程序性死亡，细胞分化。在年的头两年 在这个项目中，我们确定了两种自组装膜，细胞肌动蛋白和细胞肌动蛋白结合 Proteoglycan(CTB Proteoglycan)和一种CAM N-CAM，其分布在 心脏、功能和结构表明它们可能参与了 心脏发育。我们的长期目标是确定 这些分子和其他细胞通过它来实施这种控制 黏附分子。 我们在这个项目期间的具体目标是使用生化、细胞 生物、分子生物学和免疫组织化学技术1) CTB蛋白多糖的结构分析及其与蛋白质的关系 结构和功能，2)鉴定和表征细胞表面 与CTB相互作用的受体和细胞外基质蛋白 蛋白多糖，3)确定细胞肌动蛋白和CTB蛋白多糖的作用 心内膜细胞的迁移、增殖和分化 形成心脏间隔的垫状细胞和4)决定 一种仅见于心脏的N-CAM变异型的分布和功能 和骨骼肌。这些研究将开始阐明这些机制。 通过这些细胞黏附分子可以改变细胞的模式 迁移、细胞分裂和分化，从而影响心脏 发展。

One percent of newborn humans have some congenital heart defect, usually in the septation of the heart. Little is known, about the molecular bases for the cellular processes that drive the well-characterized series of morphological changes in heart development. Specific molecules involved in cell-substrate adhesion (SAMs) and cell-cell adhesion (CAMs) regulate morphogenesis in other systems and are correlated with developmentally- important primary processes such as cell migration, cell division, programmed cell death, cytodifferentiation. In the first two years of this project, we identified two SAMs, cytotactin and cytotactin-binding proteoglycan (CTB Proteoglycan), and a CAM, N-CAM, whose distributions in the heart, functions, and structures suggest that they may be involved in heart development. Our long-term goal is to determine the mechanisms through which this control is exerted by these molecules and other cell adhesion molecules. Our specific aims for this project period are to use biochemical, cell biological, molecular biological, and immunohistochemical techniques to 1) analyze the structure of CTB proteoglycan and the relationship of its structure and its function, 2) identify and characterize cell surface receptors and extracellular matrix proteins that interact with CTB proteoglycan, 3) determine the effects of cytotactin and CTB proteoglycan on the migration, proliferation, and differentiation of endocardial cushion cells which form the septation of the heart and 4) determine distribution and functions of a variant form of N-CAM found only in heart and skeletal muscle. These studies will begin to elucidate the mechanisms through which cell adhesion molecules can alter patterns of cell migration, cell division, and differentiation and thereby affect heart development.