Proximo-distal Patterning inthe Drosophila appendeges

果蝇附肢的近远端模式

• 批准号: 7322871
• 负责人: RICHARD S MANN
• 金额: $ 20.96万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7322871
• 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; Localized; 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

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：多细胞动物的发育需要细胞-细胞信号通路和细胞类型特异性转录因子的协调活性。在这个项目中，这些输入是如何在动物附肢的发展过程中编排将被调查。使用果蝇作为模型系统，重点是两个信号通路，无翼（Wg）和BMP同源十肢瘫痪（Dpp），如何创建腿的近端远端（PD）轴。先前的工作确定了Wg和Dpp联合收割机在沿着沿着PD轴的离散位置激活靶基因的转录。然而，这些信号如何转化为转录激活尚不清楚。使用报告基因和DNA结合分析，PD基因如何沿着PD轴被激活将被研究。第二，将采用一种新的方法来分析PD基因调控序列的染色质结构。第三，将研究细胞增殖动力学在PD基因调控中的作用。这些研究将以多种方式影响公共卫生。首先，分泌信号激活基因表达的机制在动物发育和疾病的许多方面是共同的。因此，更好地理解这些基本机制对于破译这些途径如何改变时导致癌症等疾病至关重要。第二，许多人类出生缺陷是由于附件发育中的问题。由于许多转录因子，信号分子和控制附肢发育的潜在机制在果蝇和人类之间是保守的，因此在实验强大的系统（如果蝇）中更全面地解剖这些过程可能会为这些人类出生缺陷提供重要的见解。