Developmental Genomics in C. elegans

线虫发育基因组学

• 批准号: 6743630
• 负责人: CRAIG Patrick HUNTER
• 金额: $ 30.21万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6743630
• 关键词: Caenorhabditis elegans; RNA interference; animal genetic material tag; developmental genetics; early embryonic stage; functional /structural genomics; gene expression; gene interaction; genetic regulation; helminth genetics; histogenesis; mathematical model; microarray technology; nucleic acid sequence; polymerase chain reaction; transcription factor; Caenorhabditis elegans; RNA interference; animal genetic material tag; developmental genetics; early embryonic stage; functional /structural genomics; gene expression; gene interaction; genetic regulation; helminth genetics; histogenesis; mathematical model; microarray technology; nucleic acid sequence; polymerase chain reaction; transcription factor

DESCRIPTION (provided by applicant): The long-term goal of this project is to describe and characterize in detail the pal-1 transcriptional networks that specify and pattern the C blastomere lineage in the early C. elegans embryo. The invariant development of C. elegans allowed Sulston and co-workers to describe the cell lineage of normal development. This description has proven invaluable in the analysis of developmental pathways and mechanisms. The sequencing of the nematode genome has provided the means to monitor the expression levels of all predicted genes using oligonucleotide microarrays. Here, we propose to combine these descriptive technologies and then use the powerful molecular and genetic tools available in C. elegans to characterize the transcriptional program that specifies the fate of an early embryonic blastomere.pal-1 activity is necessary and sufficient to specify the C lineage. We hypothesize thatpal-1 controls a robust gene network, the regulatory structure of which will be determined by identifying and characterizing many pal-1 target genes, particularly their upstream control regions (Aim 1). Furthermore, we hypothesize that the developmental robustness of this network is due primarily to functional redundancy of homologous target genes, but depends as well on compensating interactions within the regulatory network among non-homologous genes. RNAi of multiple genes (Aim 3) will reveal functional redundancy among homologs. To test for developmental robustness conferred by compensating regulatory interactions we will first use mathematical modeling (Aim 2) to predict the gene network architecture to identify specific non-homologous genes for similar analysis (Aim 3). This analysis, although limited to those genes that are transcriptional targets of pal-1 activity, is the necessary first step to a complete description of the activity of a master regulator.

描述（由申请人提供）：该项目的长期目标是详细描述和描述PAL-1转录网络，这些转录网络指定和对早期秀丽隐杆线虫胚胎中的C胚胎谱系进行了描述。秀丽隐杆线虫的不变发育使硫磺和同事描述了正常发育的细胞谱系。该描述在分析发展途径和机制方面已证明是无价的。线虫基因组的测序提供了使用寡核苷酸微阵列监测所有预测基因的表达水平的手段。在这里，我们建议将这些描述性技术结合起来，然后使用秀丽隐杆线虫中可用的强大分子和遗传工具来表征转录程序，该程序指定了早期胚胎胚胎的命运。PAL-1活性是必要的，足以指定C lineage。我们假设PAL-1控制着一个健壮的基因网络，其调节结构将通过识别和表征许多PAL-1靶基因，尤其是其上游控制区域来确定（AIM 1）。此外，我们假设该网络的发育鲁棒性主要是由于同源靶基因的功能冗余，但还取决于补偿非同源基因之间调节网络中的相互作用。多个基因的RNAi（AIM 3）将揭示同源物之间的功能冗余。为了测试通过补偿调节相互作用赋予的发育鲁棒性，我们将首先使用数学建模（AIM 2）预测基因网络结构以识别特定的非同源基因以进行相似的分析（AIM 3）。该分析虽然仅限于那些是PAL-1活性的转录靶标的基因，但是对主调节剂活性的完整描述的必要第一步。