DORSOVENTRAL PATTERNING THROUGH TRANSCRIPTIONAL CONTROL

通过转录控制的背腹模式

• 批准号: 6636011
• 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/6636011
• 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（改编自研究者的摘要）：拟议的研究是 旨在了解单个形态发生素如何启动复杂的层次结构 动物发育过程中导致轴规范的事件。这 正在研究的形态发生素 Dorsal 是一种转录因子 分布在背/腹核浓度梯度 果蝇胚盘胚胎。该因子既具有激活剂的作用，又具有 转录抑制子以建立基因活性的多个域 胚胎的背/腹轴。背侧功能的能力 不同的方式依赖于直接和间接的相互作用 Dorsal rel 同源结构域 (RHD) 和大量相互作用的蛋白质。一 背侧相互作用蛋白在调节背侧/腹侧发挥关键作用 模式的形成是辅阻遏物 Groucho。这个因素的作用是 同四聚体，可能介导 Dorsal 和组蛋白脱乙酰酶之间的相互作用 RPD3。具体目标是： 1) 识别 RHD 中干扰的突变 具有特定的背侧活动并利用这些突变来直接 背侧生化和发育功能之间的联系； 2） 确定 Groucho 的结构基础和发育作用 通过体外诱变、生物物理相结合的四聚化 分析和反向遗传测定； 3）确定Rpd3在其中的作用 通过新 rpd3 等位基因的表型分析 Groucho 介导的抑制， 并通过 Rpd3 的结构/功能分析，旨在表征其 Groucho交互域； 4) 表征新的 Dorsal 和 Grouchointeracting 蛋白质并通过遗传分析确定编码基因是否具有 在由 Dorsal 或 Gro 控制的发育过程中发挥重要作用。这 果蝇背侧/腹侧模式调节途径与 调节脊椎动物免疫反应和脊椎动物模式的途径 形成。因此，这些研究可能有助于更好地了解人类 免疫和发育障碍。