Genetic Analysis of Morphogenesis in a Nematode

描述(由申请者提供)：这项研究涉及如何 体内分化的细胞是在动物发育过程中产生的。每个人 分化的细胞表达一组特有的基因，作为一种 细胞命运指定过程，发生在胚胎和 胚胎后发育。编码基因的精确调控激活 决定转录因子的细胞命运对有序的细胞至关重要 命运规范流程。这项研究的目的是了解 决定转录的一个这样的细胞命运的转录激活 因子基因被指定在特定的细胞和特定的时间出现 在开发过程中。要研究的基因是Hox基因中的一员EGL-5 秀丽线虫的一科，是一种模式生物 发展研究。EGL-5决定胚胎后细胞的命运 形成成年雄性尾巴感官结构的血统。这个 激活细胞特异性顺式调节元件的转录因子 将确定EGL-5启动子。一个关键的激活剂是另一个HOX蛋白 MAb-5，它可以直接与顺式调节元件相互作用；因此，这 研究是理解lox基因级联的一个模型。MAb-5的活性是 受其他因素的监管，这些因素将被确定。正如典型的 HOX基因，EGL-5被阳性和阴性联合激活 小路。一个或多个与一个或多个负性调控部位结合的因素 顺式调控元素将被识别和描述。起作用的基因 在一个全球HOX基因调控途径中将被分离，并且功能 他们的产品进行了分析。进一步的实验将确定这些活动是如何 顺式调控元件的转录激活因子和抑制因子是 由发育时序基因控制。这项研究将有助于 了解动物发育的一个基本方面，从而有助于 克服因发育不良而引起的疾病的进展 异常现象。

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.