Control of Embryonic Polarity and Translation in C. elegans

9982944埃文斯在许多动物物种中，极化细胞分裂产生发育潜力不同的子细胞。 其中涉及的机制在很大程度上是未知的。 In C.在线虫胚胎中，极化的细胞分裂导致关键的mRNA在局部区域翻译，这反过来又在早期卵裂球之间产生差异。 glp-1 mRNA的翻译受其3'非翻译区（3' UTR）的调控元件限制于前叶细胞。 GLP-1蛋白是一种保守的膜受体，是前体发育所必需的。核心假设是glp-1 mRNA受一个调节系统控制，该系统与不对称细胞分裂有关，并对胚胎极性有贡献。对于本项目，将解决以下问题。(1)限制glp-1 mRNA翻译到胚胎前细胞的基因产物是什么？ 一种新的功能筛选将用于克隆控制GLP-1定位和早期极性的新基因。 （2）这些基因产物在控制翻译和极性中的作用是什么？ 这些基因的突变将用于检测它们在早期胚胎发生中的功能，抗体和mRNA探针将用于检测导致细胞命运调节因子在胚胎中局部表达的途径。 RNA结合分析将用于确定新蛋白质是否控制或是与glp-1 3' UTR结合并调节翻译的因子的组分。这些实验将导致发现将细胞极性和细胞分裂与mRNA翻译控制联系起来的分子网络。由于在线虫和哺乳动物之间很少有已知的组分是保守的，因此该项目可能会揭示mRNA调节和细胞特化的基本机制，这些过程对人类发育和健康至关重要。 此外，这项工作可能会导致新的策略来控制影响人类疾病的基因表达。 最后，这项工作也可能导致新的方法来控制对农业或人类健康有害的线虫寄生虫。

9982944EvansIn many animal species, polarized cells divide to generate daughter cellsthat differ in developmental potential. The mechanisms involved are largelyunknown. In C. elegans embryos, polarized cell division causes key mRNAs tobe translated in localized domains, which in turn creates differencesbetween early blastomeres. The translation of glp-1 mRNA is restricted toanterior cells by regulatory elements in its 3' untranslated region (3'UTR). GLP-1 protein is a conserved membrane receptor that is required foranterior development. The central hypothesis is that glp-1 mRNA iscontrolled by a regulatory system that is connected to asymmetric celldivision and contributes to embryonic polarity. For this project, thefollowing questions will be addressed. (1) What are the gene products thatrestrict the translation of glp-1 mRNA to anterior cells of the embryo? Anovel functional screen will be used to clone new genes that control GLP-1localization and early polarity. (2)What are the roles of these geneproducts in the control of translation and polarity? Mutations in thesegenes will be used to examine their function in early embryogenesis.Antibody and mRNA probes will be used to examine the pathways that lead tolocalized expression of cell fate regulators in the embryo. RNA bindingassays will be used to determine if new proteins control, or are components,of factors that bind to the glp-1 3' UTR and regulate translation. Theseexperiments will lead to the discovery of the molecular networks thatconnect cell polarity and cell division to the control of mRNA translation.Because the few known components are conserved between nematodes andmammals, this project will likely uncover fundamental mechanisms of mRNAregulation and cell specification, processes that are critical to humandevelopment and health. In addition, this work may lead to novel strategiesto control the expression of genes that influence human disease. Finally,this work could also lead to new ways of controlling nematode parasitesharmful to agriculture or human health.