ROLE OF THE TOLL PROTEIN IN EMBRYOGENESIS

我们的长期目标是了解 组织果蝇胚胎的背腹极性。 这 极性在受精后不久由母体基因建立 产品. 缺少任何这些母体成分的胚胎， 形成解剖结构的正常背腹模式，因为 突变胚胎的所有细胞都遵循以下发育路径： 野生型胚胎的背部或腹部细胞。 胚胎细胞 通过细胞的形态发生梯度来告知它们的背腹位置。 背侧蛋白，其结构类似于 脊椎动物原癌基因c-rel。 背侧蛋白梯度为 在合胞体胚胎中由其他11种母体基因产物组成。 遗传和分子研究表明，这些分子的功能， 跨膜信号通路，其中膜结合Toll蛋白 充当信号传导受体。 Toll蛋白分享 与许多细胞表面受体的结构特征;例如，其 胞质结构域类似于哺乳动物白细胞介素1 受体，其介导免疫应答中的许多细胞活动。 因为受调节的Toll蛋白活性对于组织细胞内的 背侧蛋白梯度和胚胎背腹极性，我们 具体目标是了解Toll蛋白的功能 生物化学和它的活动是如何在胚胎空间调节。 我们的具体目标是：1）我们将使用生化和免疫定位 定义Toll蛋白结构特性的方法， 亚细胞分布与其功能有关。2)我们将分析 野生型和突变型Toll蛋白在移植中的活性 胚胎实验和使用转染的培养细胞的细胞粘附实验 细胞，目的是调和这种蛋白质如何出现， 作为信号转导受体和细胞粘附分子。 3)我们计划通过生物化学的方法来识别那些直接与 与Toll蛋白，因为这些分子的表征将 提供线索，托尔的生化功能，以及它的活动是如何 空间调控。 这些实验也应该扩展我们的知识 参与生物化学途径的分子， 果蝇胚胎的背腹极性。

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.