Dan Wagner, PhD

Multicellular organisms possess a remarkable capacity for the development, maintenance, and regeneration of robust tissue patterns, even while facing considerable environmental and genetic challenges. Regulation of tissue patterns and the individual cell states they comprise is critical during embryonic development; failures can lead to birth defects, developmental disorders, and/or lethality. While we currently understand many of the links connecting environmental and genetic perturbations to their ultimate effects on embryos, a significant proportion of human pregnancies still result in developmental defects or miscarriages of unknown cause. At present, we also often fail to understand why certain genetic or environmental perturbations result in failed embryogenesis in some individuals, but not in others. Feedback regulation of cell fate decisions within tissues is one strategy by which developing embryos buffer a wide range of perturbations to achieve healthy outcomes. My research seeks to understand feedback mechanisms that underlie cell fate and tissue pattern robustness, as well as the disease states that arise when these mechanisms fail. My lab studies these mechanisms in the zebrafish (Danio rerio), a vertebrate species whose embryos bear considerable genetic and anatomical similarity to those of humans. As a model system, zebrafish embryos can be studied with a wide variety of reverse genetic, lineage-tracing, imaging, and molecular tools. My lab will additionally leverage single-cell genomics methods, including TRACERSEQ and STITCH, which I developed in my postdoc, to map quantitative relationships between cell lineage and cell state, in both healthy and perturbed contexts. Such analyses will also reveal transcriptional signatures for how all tissues of a developing embryo respond to perturbations, yielding candidate genes for targeted in vivo developmental genetic studies. We will additionally use comparative approaches to relate molecular details of feedback mechanisms discovered in zebrafish to their counterparts in humans.