Multi-Omic Temporal Analysis of Gene Expression in the Developing Neocortex

Our project seeks to carry out a multilevel analysis of gene regulation in the developing mouse brain, both to quantify the relative contributions of different regulatory modalities over development to final protein levels, and in order to identify factors and mechanisms underlying them. In our study thus far, we have measured gene expression in mouse neocortical tissue, over five time points encompassing the differentiation of stem cell precursors into mature cortical neurons, including steady-state mRNA levels (RNAseq), translation rates (RiboSeq), and steady-state protein levels (mass spectrometry, MS). To our knowledge, this project represents the first such time course performed in a developing tissue measuring three steps of gene expression changes simultaneously. While the use of a developing tissue as a model system presents particular challenges, such as the inability to measure protein production directly via isotope labelling, our system includes changes in cellular location, morphology, and metabolism which are critical to cortical development. These processes occur partially in response to queues from the developmental environment, and are thus difficult to model in cell culture.