Control of Embryonic Polarity and Translation in C. elegans

University Of Colorado At Denver, Aurora CO

Investigators

Abstract

9982944 Evans In many animal species, polarized cells divide to generate daughter cells that differ in developmental potential. The mechanisms involved are largely unknown. In C. elegans embryos, polarized cell division causes key mRNAs to be translated in localized domains, which in turn creates differences between early blastomeres. The translation of glp-1 mRNA is restricted to anterior cells by regulatory elements in its 3' untranslated region (3' UTR). GLP-1 protein is a conserved membrane receptor that is required for anterior development. The central hypothesis is that glp-1 mRNA is controlled by a regulatory system that is connected to asymmetric cell division and contributes to embryonic polarity. For this project, the following questions will be addressed. (1) What are the gene products that restrict the translation of glp-1 mRNA to anterior cells of the embryo? A novel functional screen will be used to clone new genes that control GLP-1 localization and early polarity. (2)What are the roles of these gene products in the control of translation and polarity? Mutations in these genes will be used to examine their function in early embryogenesis. Antibody and mRNA probes will be used to examine the pathways that lead to localized expression of cell fate regulators in the embryo. RNA binding assays 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. These experiments will lead to the discovery of the molecular networks that connect cell polarity and cell division to the control of mRNA translation. Because the few known components are conserved between nematodes and mammals, this project will likely uncover fundamental mechanisms of mRNA regulation and cell specification, processes that are critical to human development and health. In addition, this work may lead to novel strategies to control the expression of genes that influence human disease. Finally, this work could also lead to new ways of controlling nematode parasites harmful to agriculture or human health.