INTERACTION/CELL SURFACE PROTEIN--VERTEBRATE DEVELOPMENT

该计划项目的中心主题是研究 脊椎动物胚胎发育过程中的细胞表面蛋白。其中两个 这些蛋白质参与神经系统的分化。 另外两个将被测试它们在皮肤形态形成中的作用 以及骨骼的发育。这些表面蛋白是 在生物组织的三个层面上进行研究；细胞， 组织和有机体。尼罗河糖蛋白将被研究 它在调节神经细胞和新表面之间的相互作用中的作用 糖蛋白，GP90，将被研究其在 神经细胞与肌肉等非神经性组织的通讯。一个 细胞表面相关的硫酸乙酰肝素蛋白多糖将被研究 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为可能的 结构在皮肤和骨骼的形态发生中的作用。 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研究 详细地讲，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的核苷酸序列中推导出来。 他们的功能将通过确定功能 分子本身和它们与之配基的结构域 互动。人类遗传性疾病的动物模型系统 低磷症将作为一个项目的一部分进行开发，通过引入 正常等位基因的突变形式进入小鼠的生殖系。这 转基因系统将为以后的角色研究提供一个范例 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，第二个将支持分子生物学研究 将建立一个用于量化分析的行为 细胞作为正在研究的表面分子的函数。使用 这个设施将能够记录、存储和处理 细胞在定义的条件下行为，并评估其 形状和运动性作为对其他细胞或其细胞外的反应 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.