Proximo-distal Patterning inthe Drosophila appendeges

果蝇附肢的近远端模式

基本信息

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
项目类别：
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

项目摘要

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间信号通路和细胞类型特异性转录因子的协调活动。在该项目中，将研究在动物附肢发育过程中如何协调这些输入。使用果蝇作为模型系统，重点是 Wingless (Wg) 和 BMP 同源 Decapentaplegic (Dpp) 这两条信号通路如何创建腿部的近远端 (PD) 轴。先前的研究表明，Wg 和 Dpp 结合可激活 PD 轴上离散位置的靶基因转录。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，将研究 PD 基因如何沿着 PD 轴激活。其次，将采用一种新方法来分析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众健康。首先，分泌信号激活基因表达的机制对于动物发育和疾病的许多方面来说是常见的。因此，更好地理解这些基本机制对于破译这些途径在改变时如何导致癌症等疾病至关重要。其次，人类许多出生缺陷都是由于肢体发育问题造成的。由于控制附属物发育的许多转录因子、信号分子和潜在机制在果蝇和人类之间是保守的，因此在果蝇等实验强大的系统中对这些过程进行更全面的剖析可能将为这些人类出生提供重要的见解。缺陷。