Project 454828

The diversification of cell types within the developing embryo is one of the most fascinating paradigms in modern developmental biology. Starting as a fertilized egg, a series of coordinated genetic actions sequentially control cell division, differentiation, and functionalization to give rise to an embryo. Failure at any of these steps can lead to a variety of conditions such as congenital birth defects, neurodevelopmental disorders, and cancer. Yet, our global understanding of the cooperativity and synergy between the factors that coordinate embryonic development remains poorly understood. The process of development is carefully regulated by gene expression programs. The activity of genes that specify cell fate relies on a collection of proteins known as transcription factors (TFs), which engage a regulatory network code within the embryo. While the suite of TFs that exist in the embryo are known, how they function together in all cells and the regulatory code by which they act is largely unknown. To date, technical limitations in capturing the diversity of this biological process have remained a challenge; no existing technique can capture cell-to-cell differences at high resolution. I will address this knowledge gap by leveraging cutting-edge genomic tools with a powerful developmental animal model to understand how these cellular codes function during development and how they are altered in diseased states. Specifically, I will leverage recent technological advances and the powerful zebrafish model to map the TF regulatory code during embryonic development. I will apply cutting-edge single-cell genomic techniques to parse the landscape of regulatory codes that shape cells in the embryo and assess how regulatory programs are executed in clinically relevant models of developmental disorders. These results will decipher the molecular control of fate specification in an embryonic model and improve our understanding of the pathogenesis of developmental disorders.