Gene networks specifying cell lineages in a polychaete

描述（由申请人提供）：使用不对称细胞分裂是在发育过程中产生细胞类型多样性的核心。这一过程已经在秀丽隐杆线虫和黑腹果蝇中得到了广泛的遗传和分子研究。然而，这两种生物在进化上都是高度衍生的，可能是相对密切相关的。因此，如果不与一个更遥远、衍生程度更低的实验系统进行比较，就很难确定关键调控途径的保守核心成分。为此，我们建议对更接近于原始状态的双边生物——环节动物Platynereis dumerilii进行研究。这种海洋多毛动物表现出连接无脊椎动物和脊椎动物的发育特征，并提供了令人印象深刻的技术优势。在platyneris的早期胚胎发生过程中，典型的不对称细胞分裂产生不同的创始细胞系，例如称为4d的中胚层细胞系。可以很容易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。为了确定早期发育的重要调控因子，我们建议建立dumerilii EST文库和原位数据库，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来研究不对称细胞分裂和神经系统发育，并将其作为一种比较工具来定义细胞机器中最高度保守的、功能所需的核心组件。新发现和保守的基因座也将在线虫和果蝇中进行研究。

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.