Global dynamics of mRNA accumulation and translation in embryonic development (360G-Wellcome-204832_B_16_Z)
The ability of cells to generate complex gene expression patterns is fundamental to multicellular life. While global mRNA levels can now be routinely determined using ‘omics technologies, a major gap in our knowledge is how a cell produces these mRNA levels with the correct temporal dynamics. In addition, the fate of individual mRNAs represents another variable that is rarely globally considered. Therefore, the overarching question addressed in this proposal is: How are global mRNA accumulation dynamics and translatability harmonised with developmental timing to control cell fate decisions? We will exploit the rapid development and tractability of Drosophila to address this question in a developing embryo. We will model the dynamics of mRNA synthesis, processing and degradation across early embryogenesis and integrate these data with the export efficiency and translatability of mRNAs. For individual mRNAs the dynamics will be validated in vivo using live imaging and modeled to give single cell spatiotemporal resolution. For key developmental genes we will perturb mRNA production rates and translatability to determine the effect on protein function and the accuracy and robustness of dorsal-ventral patterning. Overall our data will reveal how dynamic regulation at every step in the gene expression pathway drives developmental patterning.
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