Single cell quantification of translation control in early mouse development
NIH
UNIVERSITY OF TEXAS AT AUSTIN
The initial stages of vertebrate embryo development proceed in the absence of transcription. Consequently, protein abundance of preimplantation embryos is regulated by post-transcriptional gene expression programs. In particular, new protein synthesis is required for productive embryogenesis as inhibition of translation prevents activation of the zygotic genome and leads to arrested development. Despite this critical function, translational dynamics in single mammalian embryos have remained unexplored due to technological limitations. To address this critical gap and technological need, we propose to comprehensively and quantitatively determine the dynamics of translational control during early mouse development at single nucleotide and single embryo resolution. The proposed research will apply a transformative technology that my lab developed enabling the measurement of translation in single preimplantation embryos. In this study, we will determine allele-specific ribosome engagement of mRNAs and characterize the underlying mechanisms. The proposed study will be significant as it will be the first transcriptome-wide characterization of translational control in preimplantation mammalian development at single embryo resolution and will reveal how the early embryo executes specific gene expression programs to shape its proteome. This proposal will employ an innovative ribosome profiling method to comprehensively characterize translation dynamics in mouse preimplantation development at the single cell and single embryo resolution. The proposed research will advance our understanding of fundamental processes that control gene expression in mammalian preimplantation development and may ultimately lead to new insights for mitigating the frequent errors that result in birth defects.
Non-SBIR/STTR