DORSOVENTRAL PATTERNING THROUGH TRANSCRIPTIONAL CONTROL

通过转录控制的背腹模式

• 批准号: 6386002
• 负责人: ALBERT J COUREY
• 金额: $ 28.24万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-08-07 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6386002
• 关键词: Drosophilidae; X ray crystallography; amidohydrolases; biochemical evolution; developmental genetics; gene induction /repression; intermolecular interaction; mutant; point mutation; polymerization; protein protein interaction; protein purification; transcription factor; transfection; yeast two hybrid system

DESCRIPTION (adapted from investigator's abstract): The proposed studies are aimed at understanding how a single morphogen initiates the complex hierarchy of events leading to axis specification during animal development. The morphogen under investigation, Dorsal, is a transcription factor that is distributed in a dorsal/ventral nuclear concentration gradient in the Drosophila blastoderm embryo. This factor functions as both an activator and a repressor of transcription to establish multiple domains of gene activity along the dorsal/ventral axis of the embryo. The ability of Dorsal to function in diverse ways is dependent upon direct and indirect interactions between the Dorsal rel homology domain (RHD) and a large array of interacting proteins. One Dorsalinteracting protein that plays a key role in regulating dorsal/ventral pattern formation is the corepressor Groucho. This factor, which functions as a homotetramer, may mediate an interaction between Dorsal and histone deacetylase Rpd3. The specific aims are to: 1) Identify mutations in the RHD that interfere with specific Dorsal activities and utilize these mutations to make direct links between the biochemical and developmental functions of Dorsal; 2) Determine the structural basis and developmental role of Groucho tetramerization through a combination of in vitro mutagenesis, biophysical analysis, and reverse genetic assays; 3) Determine the role of Rpd3 in Grouchomediated repression through the phenotypic analysis of new rpd3 alleles, and through a structure/function analysis of Rpd3 aimed at characterizing its Grouchointeraction domain; 4) Characterize new Dorsal and Grouchointeracting proteins and determine, via genetic analysis, if the encoding genes have important roles in the developmental processes governed by Dorsal or Gro. The pathway regulating dorsal/ventral patterning in Drosophila is homologous to pathways regulating the vertebrate immune response and vertebrate pattern formation. Thus, these studies may lead to a better understanding of human immunological and developmental disorders.

描述（根据研究者的摘要进行了改编）：拟议的研究是 旨在了解单个形态学如何启动复杂层次结构 导致动物发育过程中轴心规格的事件。这 正在研究的形态学，背侧是转录因子，是 分布在背侧/腹侧核浓度梯度中 果蝇胚胚胚。该因素既可以作为激活因子，又是 转录的阻遏物沿着基因活性建立多个域 胚胎的背/腹轴。背侧功能的能力 各种方式取决于直接和间接相互作用 背相关同源域（RHD）和大量相互作用的蛋白质。一 背裂蛋白在调节背部/腹侧起关键作用 图案形成是Corepressor groucho。这个因素，起作用 同型酯可能会介导背和组蛋白脱乙酰基酶之间的相互作用 RPD3。具体目的是：1）识别RHD中的突变 通过特定的背面活动，并利用这些突变来直接 背侧的生化和发育功能之间的联系； 2） 确定Groucho的结构基础和发展作用 通过体外诱变的结合，生物物理的结合 分析和反向遗传测定； 3）确定RPD3在 通过对新的RPD3等位基因的表型分析进行的抑制作用， 通过RPD3的结构/功能分析，旨在表征其 grouchoInteraction域； 4）表征新的背和grouchointracting 蛋白质并通过遗传分析确定编码基因是否具有 在由背面或GRO管辖的发展过程中的重要作用。这 果蝇中调节背或腹侧图案的途径与 调节脊椎动物免疫反应和脊椎动物模式的途径 形成。因此，这些研究可能导致对人类的更好理解 免疫学和发育障碍。