TOLL PROTEIN AND EMBRYOGENESIS

我们的长期目标是了解 组织果蝇胚胎的背腹两极。这 受精后不久，母体基因就会建立起两极 产品。缺少这些母体成分中的任何一个的胚胎无法 形成正常的解剖结构的背腹模式，因为 突变胚胎的所有细胞都遵循其中一种的发育路径 野生型胚胎的背侧或腹侧细胞。胚胎细胞是 它们的背腹位置由形态因子梯度决定 背部蛋白，它在结构上类似于 脊椎动物原癌基因c-rel。背部的蛋白质梯度是 在合胞胚胎中由其他11个母体基因产物组织。 遗传和分子研究表明，这些分子在 膜结合Toll蛋白的跨膜信号转导途径 充当信号转导受体。Toll蛋白股票 具有许多细胞表面受体的结构特征；例如，其 细胞质结构域类似于哺乳动物的白介素1 受体，它在免疫反应中介导许多细胞活动。 因为受调控的Toll蛋白活性对于组织 背侧蛋白梯度，因此胚胎背侧-腹侧极性，我们的 具体目标是了解Toll蛋白的功能 以及它的活性在胚胎中是如何被空间调控的。 我们的具体目标是：1)使用生化和免疫定位 确定Toll蛋白结构性质的方法和 与其功能相关的亚细胞分布。2)我们将化验 野生型和突变型Toll蛋白在移植中的活性 转基因培养的胚胎和细胞内黏附的实验 细胞，目的是协调这种蛋白质如何表现为 既是信号转导受体，又是细胞黏附分子。 3)我们计划从生物化学的角度识别直接相互作用的分子 Toll蛋白，因为这些分子的特征 为Toll的生化功能及其活性提供线索 在空间上受到限制。这些实验也应该扩大我们的知识 参与生物化学途径的分子组成 果蝇胚胎的背腹两极。

Our long-term objective is to understand the biochemical pathway that organizes dorsal-ventral polarity of the Drosophila embryo. This polarity is established shortly after fertilization by maternal gene products. An embryo missing any of these maternal components fails to form the normal dorsal-ventral pattern of anatomical structures, because all cells of the mutant embryo follow the developmental path of either dorsal or ventral cells of the wild type embryo. Embryonic cells are informed of their dorsal-ventral positions by a morphogen gradient of the dorsal protein, which is structurally similar to the product of the vertebrate proto-oncogene c-rel. The dorsal protein gradient is organized in the syncytial embryo by 11 other maternal gene products. Genetic and molecular studies suggest that these molecules function in a transmembrane signaling pathway in which the membrane-bound Toll protein acts as a signal transducing receptor. The Toll protein shares structural features with many cell surface receptors; for example, its cytoplasmic domain is similar to that of the mammalian interleukin 1 receptor, which mediates many cellular activities in the immune response. Because regulated Toll protein activity is critical for organizing the dorsal protein gradient and hence embryonic dorsal-ventral polarity, our specific goal is to understand how the Toll protein functions biochemically and how its activity is spatially regulated in the embryo. Our specific aims are: 1) We will use biochemical and immuno-localization methods to define the Toll protein's structural properties and subcellular distribution relevant to its functioning. 2) We will assay the activities of wild type and-mutant Toll proteins in transplantation experiments with embryos and in cell adhesion using transfected cultured cells, with the aim of reconciling how this protein could appear to function as both signal transducing receptor and cell adhesion molecule. 3) We plan to identify biochemically molecules that directly interact with the Toll protein, since characterization of these molecules will provide clues to Toll's biochemical function and how its activity is spatially regulated. These experiments should also expand our knowledge of the molecules involved in the biochemical pathway that organizes dorsal-ventral polarity of the Drosophila embryo.