Gene networks specifying cell lineages in a polychaete

描述（由申请方提供）：使用不对称细胞分裂是开发期间产生细胞类型多样性的关键。这一过程已被广泛研究的遗传和分子方法在秀丽隐杆线虫和果蝇。然而，这两种生物在进化上都是非常高级的，并且可能相对密切相关。因此，它是很难定义保守的核心组件的关键调控途径，而不比较一个更遥远的相关和较少衍生的实验系统。为此，我们建议启动研究的bilaterian生物更可能类似于一个原始的状态，环节动物Platynereis dumerilii。这种海洋多毛类动物具有连接无脊椎动物和脊椎动物的发育特征，并提供令人印象深刻的技术优势。在Platynereis的早期胚胎发生过程中，刻板的不对称细胞分裂产生不同的创始人细胞谱系，如称为4d的中胚层细胞谱系。可以很容易地获得数千个同步的胚胎阶段，胚胎是透明的，并且可以使用RNA干扰来降低基因功能。为了确定早期发育的重要调控因子，我们建议建立一个杜氏青霉EST文库和一个原位数据库，并使用亲本dsRNA干扰和靶基因的特异性抑制剂来研究基因需求。我们也将利用微阵列技术来检测突变胚胎中基因表达的整体变化。我们的目标是探索和利用这个新的模型系统的不对称细胞分裂和神经系统发育的研究，并使用它作为一个比较工具，定义最高度保守的，功能上所需的核心组件的细胞机器。新发现的和保守的基因座也将在C.线虫和果蝇。

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.