CELL-CELL AND -MATRIX ADHESION IN CARDIAC MORPHOGENESIS

百分之一的新生儿有先天性心脏缺陷，通常 在心脏的分隔处。 关于分子基础知之甚少 对于驱动一系列特征鲜明的细胞过程， 心脏发育的形态学变化。 涉及的特定分子 在细胞-基质粘附（SAM）和细胞-细胞粘附（CAM）调节中， 在其他系统中的形态发生，并与发育相关- 重要的初级过程如细胞迁移，细胞分裂， 程序性细胞死亡细胞分化 前两年 在这个项目中，我们鉴定了两种SAM，细胞粘附素和细胞粘附素结合 蛋白聚糖（CTB Proteoglycan）和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 这些分子和其它细胞通过这些通道来进行这种控制 粘附分子 我们在这个项目期间的具体目标是利用生物化学，细胞， 生物学、分子生物学和免疫组织化学技术，以1） 分析CTB蛋白聚糖的结构及其与蛋白质的相互关系， 结构和功能，2）识别和表征细胞表面 与CTB相互作用的受体和细胞外基质蛋白 3）测定细胞毒素和CTB蛋白聚糖的作用 对内皮细胞迁移、增殖和分化的影响 形成心脏分隔的垫细胞和4）决定 仅在心脏中发现的N-CAM变体的分布和功能 和骨骼肌。 这些研究将开始阐明 细胞粘附分子可以通过它改变细胞 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.