Genetic Analysis of Morphogenesis in a Nematode

描述（由申请人提供）：本研究涉及如何 身体的分化细胞是在动物发育过程中产生的。每个 分化的细胞表达一组特征性的基因，这是一种 细胞命运的规范过程发生在胚胎和 胚后发育精确调控的基因激活 细胞命运决定转录因子对有序的细胞 命运规范过程。这项研究的目的是了解如何 一种这样的细胞命运决定转录的转录激活 因子基因被指定在特定的细胞和特定的时间发生 在发展过程中。待研究的基因是egl-5，它是Hox基因的成员 线虫秀丽隐杆线虫科，一种模式生物， 发展研究egl-5决定胚后细胞的命运 产生成年雄性尾巴感觉结构的血统。的 激活细胞特异性顺式调节元件的转录因子， 将鉴定EGL-5启动子。一个关键的激活因子是另一种Hox蛋白 MAB-5，其可与顺式调节元件直接相互作用;因此， 研究可作为了解lox基因级联的模型。MAB-5活性是 受其他因素的调节，这些因素将被确定。作为典型的 Hox基因，egl-5是激活的组合，积极和消极的 途径。一个或多个因子结合到细胞内的负调控位点， 将鉴定和表征顺式调节元件。基因作用 在一个全球性的Hox基因调控途径将被分离和功能， 他们的产品分析。进一步的实验将确定这些活动是如何 转录激活因子和抑制因子的顺式调节元件是 由发育定时基因控制这项研究将有助于 了解动物发展的基本方面，从而有助于 在克服因发展而引起的疾病方面取得的进展 异常

DESCRIPTION (provided by applicant): This research concerns how the differentiated cells of the body are produced during animal development. Each differentiated cell expresses a characteristic set of genes as a result of a cell fate specification process that takes place during embryonic and postembryonic development. Precisely regulated activation of genes encoding cell fate determining transcription factors is critical to the orderly cell fate specification process. The aim of this research is to understand how transcriptional activation of one such cell fate determining transcription factor gene is specified to occur in a particular cell and at a particular time during development. The gene to be studied is egl-5, a member of the Hox gene family of the nematode Caenorhabditis elegans, a model organism for developmental studies. egl-5 determines cell fates in a postembryonic cell lineage that gives rise to sensory structures of the adult male tail. The transcription factors that activate a cell-specific cis-regulatory element from the egl-5 promoter will be identified. One key activator is another Hox protein MAB-5, which may interact directly with the cis-regulatory element; thus, this research serves as a model to understand a lox gene cascade. MAB-5 activity is regulated by additional factors, which will be identified. As is typical for Hox genes, egl-5 is activated by a combination of both positive and negative pathways. A factor or factors that bind to a negative regulatory site within the cis-regulatory element will be identified and characterized. Genes acting in a global Hox gene regulatory pathway will be isolated and the functions of their products analyzed. Further experiments will determine how the activities of transcriptional activators and repressors of the cis-regulatory element are controlled by developmental timing genes. This research will contribute to understanding a fundamental aspect of animal development, and thus help towards progress in overcoming diseases that arise as a result of developmental abnormalities.