Mechanisms of translational control during embryogenesis

Embryogenesis is a rapid and precisely orchestrated process during which genes must be expressed at the right time and place. After fertilization, gene expression control is handed over from maternal determinants – mRNAs and proteins deposited in the egg – to zygotic determinants – newly synthesized zygotic mRNAs. As the embryo enters gastrulation, cells continue to rely on changes in gene expression to instruct cell fate transitions.

At its core, gene expression involves the synthesis of mRNA molecules that are subsequently translated into functional proteins in a tightly regulated manner. In the lab, we focus on asking how mRNA translation is coordinated during these fascinating developmental transitions to regulate the expression of proteins required for growth and cellular differentiation.

To address this question at a systematic level during vertebrate embryonic development, we combine the power of the zebrafish model with high-throughput sequencing, massively parallel reporter and proteomics approaches. We complement them with biochemical, genetic and in vivo imaging experiments to gain mechanistic insights. Specifically, we focus on:

Regulation at the translation initiation step: What is the role of 5′ UTR motifs? Which RNA-binding proteins are recruited to regulate initiation? What are their functions in development?

Proteome diversification: How do 5′ UTR isoforms contribute to proteoform diversity as cells differentiate?