EMBRYONIC DORSOVENTRAL POLARITY IN DROSOPHILA

果蝇胚胎背腹极性

• 批准号: 6385816
• 负责人: CARL HASHIMOTO
• 金额: $ 32.67万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6385816
• 关键词: Drosophilidae; biological signal transduction; cell membrane; cellular polarity; early embryonic stage; enzyme activity; gene mutation; genetically modified animals; immunoprecipitation; invertebrate embryology; protein structure function; serine proteinases; western blottings

DESCRIPTION: (Verbatim from the applicant's abstract) Dorsoventral polarity of the Drosophila embryo is established by local activation of the Toll signaling pathway. The membrane receptor Toll appears to be activated by an extracellular ligand that is localized to the ventral side of the embryo. The Toll ligand is generated by a proteolytic processing reaction which requires four members of the serine protease family encoded by the nudel, gastrulation defective (gd), snake, and easter genes. Earlier genetic studies suggested that these proteases act in a sequential activation cascade in which the final protease processes the Toll ligand precursor, and that activation of proteases in this cascade is ventrally localized, thereby spatially restricting production of the Toll ligand. Our more recent studies suggest that the pathway producing the Toll ligand is regulated at multiple steps so that the Toll ligand is generated at an appropriate level and at a defined time and space during embryonic development. Our major goal is to understand how the proteases required to produce the Toll ligand are organized into a pathway and how they are activated and regulated. Our specific aims are: 1) To test if the proteases act in a sequential activation cascade and if the activation of any of the proteases is spatially regulated, by biochemica1 analysis of the proteases in vivo; 2) To determine if the proteases are activated on the embryo surface and if activation is spatially restricted, using immunolocalization methods; 3) To decipher the role of the GD protein in the pathway, through a combination of molecular genetic and biochemical experiments; and 4) To identify factors that spatially control the activity of the Snake and Easter proteases, using biochemical and genetic approaches. Recent studies suggest that the ancestral role of the Toll signaling pathway is in host defense, to recognize and signal the presence of microbial pathogens, and is shared by the immune systems of insects and mammals. The signal that acts as the ligand for Toll in mammalian immunity, or how this signal is generated, is not known. Thus, the information obtained from our proposed studies should be of significant relevance for addressing the question of how the Toll signaling pathway is activated during the immune response.

描述：（逐字摘自申请人的摘要）背腹极性 果蝇胚胎是通过局部激活 Toll 信号传导建立的 途径。膜受体 Toll 似乎被细胞外激活 位于胚胎腹侧的配体。 Toll 配体是 由蛋白水解加工反应产生，需要四个成员 由 nudel、原肠胚形成缺陷 (gd) 编码的丝氨酸蛋白酶家族， 蛇和复活节基因。早期的遗传学研究表明这些蛋白酶 在顺序激活级联中起作用，其中最终的蛋白酶处理 Toll配体前体，并且该级联中蛋白酶的激活是 腹侧局部化，从而在空间上限制了 Toll 的产生 配体。我们最近的研究表明，产生收费的途径 配体在多个步骤中受到调节，以便 Toll 配体在 在胚胎时期的适当水平和规定的时间和空间 发展。我们的主要目标是了解蛋白酶如何 Toll 配体的产生、组织成途径以及它们是如何被激活的 并受到监管。我们的具体目标是： 1) 测试蛋白酶是否在一定范围内发挥作用 顺序激活级联并且如果任何蛋白酶的激活是 通过体内蛋白酶的生化分析进行空间调节； 2) 至 确定胚胎表面的蛋白酶是否被激活以及是否 使用免疫定位方法，激活在空间上受到限制； 3) 至 通过结合以下方法破译 GD 蛋白在该途径中的作用 分子遗传学和生化实验； 4) 确定因素 使用空间控制蛇蛋白酶和复活节蛋白酶的活性 生物化学和遗传学方法。最近的研究表明，祖先 Toll 信号通路的作用是在宿主防御中识别和发出信号 微生物病原体的存在，并且由免疫系统共享 昆虫和哺乳动物。哺乳动物中充当 Toll 配体的信号 免疫性或该信号是如何产生的尚不清楚。因此，信息 从我们提出的研究中获得的结果应该与 解决Toll信号通​​路在过程中如何被激活的问题 免疫反应。