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MAP kinase signal specificity in the C. elegans germline

线虫种系中的 MAP 激酶信号特异性

基本信息

批准号：
7172689
负责人：
VALERIE J REINKE
金额：
$ 27.28万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-02-01 至 2008-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7172689
关键词：
Affect Algorithms Animals Binding Biochemical Biochemical Genetics Biological Assay Caenorhabditis elegans Cell Cycle Cell Cycle Progression Cell Proliferation Cells DNA Microarray Chip DNA Microarray format Defect Development Duct (organ) structure Functional RNA Gene Expression Gene Targeting Genes Genetic Genetic Transcription Germ Cells Germ Lines Goals Immediate-Early Genes Individual Knowledge Lead MAP Kinase Modules MAP Kinase Signaling Pathways Malignant Neoplasms Mediating Meiosis Microarray Analysis Mitogen-Activated Protein Kinases Molecular Analysis Molecular Genetics Molecular Profiling Myoblasts Pathway interactions Phenotype RAS genes Regulation Regulatory Element Reporter Sexual Development Signal Pathway Signal Transduction Site Specificity Testing Tissues Transgenes Transgenic Organisms base cell type chromatin immunoprecipitation functional genomics gain of function genetic analysis in vivo loss of function migration mutant research study response transcription factor

项目摘要

DESCRIPTION (provided by applicant): Signaling pathways such as the MAP kinase pathway are used in many different tissues throughout metazoan development to control important cell fate decisions. Misinterpretation of a signal by a cell can lead to cancer or developmental defects. However, the mechanisms by which a signal directs downstream effectors to generate the ultimate fate of the cell remain largely mysterious. The long-term objective of this proposal is to gain a comprehensive knowledge of how the information from a cytoplasmic signal such as MAP kinase is interpreted through altered target gene expression to produce a specific cell fate. These studies focus on MAP kinase regulation of meiotic progression in the Caenorhabditis elegans germ line. Because MAP kinase mediates meiotic progression in many species, the results obtained from these studies will potentially be broadly applicable. By taking functional genomics approaches to identify genes acting downstream of the MAP kinase signaling pathway, followed by classical molecular analysis of key effeetors, comprehensive knowledge of the genetic and biochemical network responding to MAP kinase in a particular tissue will be attained. Specifically, DNA microarrays will be used to identify candidate transcriptional target genes downstream of MAP kinase signaling in the C. elegans germ line. The cis-acting regulatory sites in those genes will be defined through sequence identification algorithms and tested for MAP kinase responsiveness through transgenic analysis. Candidate immediate-early genes encoding transcription factors will then be examined for binding to the cis-acting sites identified in the target genes. The requirement for these downstream effectors, whether transcription factor or transcription target, in mediating MAP kinase dependent meiotic progression in vivo will be assessed using RNA-mediated interference and genetic analysis. Together these experiments should build toward a comprehensive understanding of the mechanisms used to produce a specific cell fate in response to a generally used signaling pathway.

描述（由申请人提供）：在后生动物发育过程中，许多不同的组织都使用MAP激酶途径等信号通路来控制重要的细胞命运决定。细胞对信号的误解会导致癌症或发育缺陷。然而，信号引导下游效应器产生细胞最终命运的机制在很大程度上仍然是神秘的。本研究的长期目标是全面了解来自细胞质信号（如MAP激酶）的信息如何通过改变靶基因表达来解释，从而产生特定的细胞命运。这些研究集中在MAP激酶对秀丽隐杆线虫生殖系减数分裂过程的调控上。由于MAP激酶在许多物种中介导减数分裂过程，因此这些研究结果可能具有广泛的适用性。通过功能基因组学方法鉴定作用于MAP激酶信号通路下游的基因，然后对关键效应物进行经典分子分析，将获得对特定组织中MAP激酶响应的遗传和生化网络的全面了解。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

DPL-1 (DP) acts in the germ line to coordinate ovulation and fertilization in C. elegans.

DPL-1（DP）在种植线上起作用，以协调秀丽隐杆线虫的排卵和施肥。

DOI：
10.1016/j.mod.2009.01.008
发表时间：
2009-05
期刊：
MECHANISMS OF DEVELOPMENT
影响因子：
2.6
作者：
Chi, Woo;Reinke, Valerie
通讯作者：
Reinke, Valerie

Promotion of oogenesis and embryogenesis in the C. elegans gonad by EFL-1/DPL-1 (E2F) does not require LIN-35 (pRB).

DOI：
10.1242/dev.02490
发表时间：
2006-08-01
期刊：
Development (Cambridge, England)
影响因子：
0
作者：
Chi, Woo;Reinke, Valerie
通讯作者：
Reinke, Valerie

C. elegans nucleostemin is required for larval growth and germline stem cell division.

秀丽隐杆线虫核苷酸是幼虫生长和种系干细胞分裂所必需的。

DOI：
10.1371/journal.pgen.1000181
发表时间：
2008-08-22
期刊：
PLOS GENETICS
影响因子：
4.5
作者：
Kudron, Michelle M.;Reinke, Valerie
通讯作者：
Reinke, Valerie

Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase.

I 类组蛋白脱乙酰酶对组织特异性和细胞外基质相关基因的调节。

DOI：
10.1016/j.molcel.2005.04.006
发表时间：
2005
期刊：
Molecular cell.
影响因子：
0
作者：
Whetstine,JohnathanR;Ceron,Julian;Ladd,Brendon;Dufourcq,Pascale;Reinke,Valerie;Shi,Yang
通讯作者：
Shi,Yang