Gene networks specifying cell lineages in a polychaete

指定多毛类细胞谱系的基因网络

• 批准号: 6929012
• 负责人: BRUCE A BOWERMAN
• 金额: $ 27.35万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929012
• 关键词: Annelida; RNA interference; aquatic organism; cadherins; cell cycle; developmental genetics; early embryonic stage; endoderm; functional /structural genomics; gene expression; mesoderm; microarray technology; mutant

DESCRIPTION (provided by applicant): The use of asymmetric cell division is central to generating cell type diversity during development. This process has been studied extensively using genetic and molecular approaches in both Caenorhabditis elegans and Drosophila melanogaster. However, both of these organisms are evolutionarily very high derived and may be relatively closely related. Thus it is difficult to define conserved core components of key regulatory pathways without comparison to a more distantly related and less derived experimental system For this purpose, we propose to initiate studies of a bilaterian organism more likely to resemble a primitive state, the annelid Platynereis dumerilii. This marine polychaete exhibits developmental features that link invertebrates and vertebrates, and provides impressive technical advantages. During early embryogenesis of Platynereis stereotypic asymmetric cell divisions generate distinct founder cell lineages, such as a mesodermal cell lineage called 4d. Thousands of synchronous embryonic stages can be easily obtained, the embryos are transparent and gene function can be reduced using RNA interference. To identify important regulators of early development, we propose to generate a P. dumerilii EST library and an in situ data base, and to examine gene requirements using both parental dsRNA interference and specific inhibitors of target genes. We also will employ microarray techniques to examine global changes in gene expression in mutant embryos. Our goals are to explore and exploit this new model system for studies of asymmetric cell division and nervous system development, and to use it as a comparative tool for defining the most highly conserved, functionally required core components of cellular machineries. Newly discovered and conserved loci will also be studied in C. elegans and Drosophila.

描述（由申请人提供）：不对称细胞分裂的使用对于在发育过程中产生细胞类型多样性至关重要。在秀丽隐杆线虫和果蝇果蝇中，使用遗传和分子方法对这一过程进行了广泛的研究。但是，这两种生物在进化上都是非常高的衍生，并且可能相对密切相关。因此，很难定义关键调节途径的保守核心成分，而没有与此目的的更遥远相关和衍生的实验系统进行比较，我们建议启动对幼虫生物体的研究，更可能类似于原始状态，即Annelid platyneriis dumeriliiii dumeriliii dumeriliii 。这款海洋多齿素具有将无脊椎动物和脊椎动物联系起来的发育特征，并提供了令人印象深刻的技术优势。在早期胚胎刻板印象不对称细胞分裂的早期胚胎发生过程中，会产生不同的创建者细胞谱系，例如中胚层细胞谱系，称为4D。可以轻松地获得数千个同步胚胎阶段，胚胎是透明的，并且可以使用RNA干扰降低基因功能。为了确定早期发展的重要调节因子，我们建议生成杜米利菌Est库和原位数据库，并使用父母DSRNA干扰和靶基因的特定抑制剂检查基因需求。我们还将采用微阵列技术来检查突变胚胎中基因表达的全局变化。我们的目标是探索和利用这种新的模型系统，以研究不对称的细胞分裂和神经系统发育，并将其用作定义细胞机械的最高保守，功能最高，功能最高的核心组件的比较工具。新发现和保守的基因座也将在秀丽隐杆线虫和果蝇中进行研究。