INTERACTION/CELL SURFACE PROTEIN--VERTEBRATE DEVELOPMENT

该项目的中心主题是研究 细胞表面蛋白在脊椎动物胚胎发育中的作用。两 这些蛋白质参与神经系统的分化 另外两种将被测试它们在皮肤形态发生中的作用 以及骨骼的发育。这些表面蛋白是 在生物组织的三个层次上进行研究;细胞， 组织和有机体。将研究NILE糖蛋白， 它在调节神经细胞之间的相互作用中的作用， 糖蛋白，GP 90，将被研究其功能， 神经细胞与非神经元组织如肌肉的通讯。一 将研究细胞表面相关硫酸乙酰肝素蛋白聚糖， 它在胚胎皮肤和膜的形态发生中的作用 糖蛋白碱性磷酸酶将被考虑用于可能的 在皮肤和骨骼的形态发生中的结构作用。 所有项目都将使用最新的重组DNA方法 技术、免疫学、蛋白质化学和细胞生物学来研究 这些表面蛋白的结构和功能， 与脊椎动物的发育高度相关。蛋白质的结构 将从编码它们的cDNA的核苷酸序列推断。 将通过确定其功能来研究其功能 结构域的分子本身和配体与他们 互动.人类遗传性疾病的动物模型系统 hypophosphatasia将作为一个项目的一部分，通过引入 正常等位基因的突变形式进入小鼠的生殖系。这 转基因系统将作为一个范例，为以后的研究的作用 其他细胞表面分子在脊椎动物发育中的作用 胚胎将为该计划建立两个核心设施 项目一个将支持分子生物学研究， 将建立一个定量分析的行为， 细胞作为一个功能的表面分子正在研究。与 这个设施，我们将能够记录，存储和处理图像的 细胞在规定条件下的行为，并评估其 形状和运动作为对其他细胞或其细胞外 矩阵

The central theme of this program project is the study of interactions of cell surface proteins in the development of the vertebrate embryo. Two of these proteins are involved in the differentiation of the nervous system and two others will be tested for their role in the morphogenesis of skin and the development of the bony skeleton. These surface proteins are being investigated at three levels of biological organization; the cell, the tissue and the organism. The NILE glycoprotein will be studied for its role in mediating interactions between nerve cells, and a new surface glycoprotein, GP90, will be investigated for its function in the communication of nerve cells with non-neuronal tissues such as muscle. A cell surface-associated heparan sulfate proteoglycan will be studied for its role in the morphogenesis of the embryonic skin, and the membrane glycoprotein alkaline phosphatase will be considered for a possible structural role in the morphogenesis of the skin and the bony skeleton. All projects will use the most up-to-date methods in recombinant DNA technology, immunology, protein chemistry and cell biology to investigate in detail the structure and function of these surface proteins that are highly relevant to vertebrate development. The structure of the proteins will be deduced from the nucleotide sequence of cDNAs that encode them. Their functions will be investigated by identifying the functional domains on the molecules themselves and of the ligands with which they interact. An animal model system for the human inherited disorder hypophosphatasia will be developed as part of one project by introducing mutated forms of the normal allele into the germ line of mice. This transgenic system will serve as a paradigm for later studies on the role of the other cell surface molecules in the development of vertebrate embryos. Two core facilities will be established for this program project. One will support the molecular biological studies and the second one will be established for the quantitative analysis of the behavior of cells as a function of the surface molecules that are being studied. With this facility we will be able to record, store and process images of cells behaving under defined conditions and evaluate changes in their shape and motility as a response to other cells or their extracellular matrix.