Control of Embryonic Polarity and Translation in C. elegans

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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.