During animal development, generation of different cell types requires that specific proteins become active only in specific cells at specific times. Many of the mRNAs that make these proteins are precisely regulated within the cell cytoplasm. These mRNAs form complexes (mRNPs) with numerous regulatory proteins that dictate rates of protein synthesis, mRNA localization, and mRNA destruction. Developmental controls must modulate these mRNP complexes, but how this is achieved is essentially a mystery. This project will explore this issue in the nematode C. elegans, a powerful experimental system. During early C. elegans development, multiple RNA-binding proteins control specific mRNPs at distinct developmental stages. Recent studies revealed that these mRNPs undergo remarkable and complex transformations during oocyte differentiation and early embryogenesis. This project's goals are to explore how these transformations arise and to understand how developmental pathways control them. The dynamic behavior of specific mRNP components will be examined directly in oocytes and embryos by tagging mRNAs and proteins with fluorescent molecules that can be seen with high-resolution microscopes. Disruption of both known and unknown genes will be done to explore how known developmental pathways influence mRNP behavior and to discover new mRNP regulators. These experimental methods can be powerfully combined in C. elegans, but not in most other organisms. Furthermore, because all C. elegans mRNP components found to date have counterparts in humans and other metazoans, this study will likely yield new insights into fundamental mechanisms common to most multicellular species including humans. In addition, this work may lead to new tools for controlling genes important for human, animal, and plant disease. Finally, this project will provide scientific training for graduate and undergraduate students, and will contribute to a high school science outreach program.
