Proximo-distal Patterning inthe Drosophila appendeges

果蝇附肢的近远端模式

• 批准号: 7926138
• 负责人: RICHARD S MANN
• 金额: $ 16.05万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7926138
• 关键词: Address; Adult; Animals; Anterior; Be++ element; Beryllium; Biological Models; Cell Proliferation; Chromatin Structure; Congenital Abnormality; DNA Binding; Data; Development; Developmental Gene; Disease; Dissection; Distal; Drosophila genus; Drosophila melanogaster; Elements; Embryo; Embryonic Development; Funding; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic Transcription; Goals; Grant; Homeostasis; Homologous Gene; Human; Indium; Leg; Life Cycle Stages; Maintenance; Malignant Neoplasms; Methods; Modeling; Molecular; Ovum; Pathway interactions; Pattern; Play; Positioning Attribute; Primordium; Process; Proteins; Public Health; Regulator Genes; Regulatory Element; Reporter Genes; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Specific qualifier value; Staging; System; Testing; Transcriptional Activation; Translating; Work; appendage; base; cell type; fly; homeodomain; imaginal disc; insight; intercellular communication; morphogens; novel; novel strategies; promoter; research study; tool; transcription factor

The development of multicellular animals requires the coordinated activities of cell-cell signaling pathways and cell-type specific transcription factors. In this project, how these inputs are orchestrated during the development of animal appendages will be investigated. Using Drosophila melanogaster as the model system, the focus is how two signaling pathways, Wingless (Wg) and the BMP homolog Decapentaplegic (Dpp), create the proximo-distal (PD) axis of the leg. Previous work established that Wg and Dpp combine to activate the transcription of target genes at discreet positions along the PD axis. However, how these signals translate to transcriptional activation is not understood. Using reporter gene and DNA binding analyses, how PD genes are activated along the PD axis will be investigated. Second, a novel method to analyze the chromatin structure of PD gene regulatory sequences will be employed. Third, the role that cellular proliferation dynamics play in PD gene regulation will be investigated. These studies will impact public health in several ways. First, the mechanism by which secreted signals activate gene expression is common to many aspects of animal development and disease. Thus, a better understanding of these basic mechanisms is critical for deciphering how these pathways, when altered, contribute to diseases such as cancer. Second, many human birth defects are due to problems in the development of the appendages. As many of the transcription factors, signaling molecules, and underlying mechanisms controlling appendage development are conserved between Drosophila and humans, it is likely that a more comprehensive dissection of these processes in an experimentally powerful system such as Drosophila will provide important insights into these human birth defects.

多细胞动物的发育需要细胞-细胞信号通路的协调活动 和细胞类型特异性转录因子。在此项目中，如何在 将对动物附肢的发展进行调查。以黑腹果蝇为模型 系统，关注的焦点是两个信号通路，无翼(Wg)和BMP同源物如何导致瘫痪 (DPP)，创建腿的近端-远端(PD)轴。以前的工作确定了工作组和民进党结合在一起 在PD轴上的特定位置激活靶基因的转录。然而，这些信号是如何 翻译为转录激活还不是很清楚。使用报告基因和DNA结合分析，如何 沿着PD轴被激活的PD基因将被研究。第二，一种新的分析方法 将采用染色质结构的PD基因调控序列。第三，细胞的作用 增殖动力学在PD基因调控中的作用将被研究。 这些研究将在几个方面影响公众健康。第一，释放信号的机制 激活基因表达在动物发育和疾病的许多方面都是常见的。因此，一个更好的 对这些基本机制的理解对于破译这些通路是如何在改变时， 会导致癌症等疾病。其次，许多人类的先天缺陷是由于 附肢的发育。因为许多转录因子、信号分子和潜在的 控制附肢发育的机制在果蝇和人类之间是保守的，很可能 在实验上强大的系统中对这些过程进行更全面的剖析 果蝇将为了解这些人类先天缺陷提供重要的见解。