MAP kinase signal specificity in the C. elegans germline

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。

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.