Dr. Michael Dorrity, EMBL Heidelberg, Germany
Dr. Michael Dorrity, Group Leader in the Molecular Systems unit at EMBL Heidelberg, will present: "Temperature and timing in embryonic development"
Main content
The genetic program of embryonic development is remarkably robust, but temperature can accelerate its progression and degrade its ability to generate animals with invariant anatomy. We use ultra-high throughput single cell genomics, computational methods, and cross-species comparison to disentangle the relationships between temperature, developmental rate, and the reproducibility of embryogenesis. We characterize hundreds of individual zebrafish embryos under temperature stress using whole-animal single cell RNA-seq to identify cell types and molecular programs that drive phenotypic variability. We find that temperature perturbs the normal proportions and gene expression programs of numerous cell types and introduces asynchrony in their development. The notochord is particularly sensitive to temperature stress, which we show is due to a specialized cell type, sheath cells. Without fully-functional protein homeostasis (proteostasis) machinery, sheath cells accumulate misfolded protein at elevated temperature, leading to a cascading structural failure of the notochord and anatomic defects in the embryo. In recent work, we find that collagen synthesis pushes other cell types beyond their proteostatic limits as temperature increases, leading to aggregation of collagen in the developing jaw. Using a combination of quantitative proteomics and sci-RNA-seq, we identify a key protein modification as a driver of robustness development and function of these cells. Aside from direct effects of temperature on protein homeostasis, our group is exploring how the indirect effect of developmental acceleration influences the robustness of development in different fish species. We focus on cell type-specific differentiation dynamics in a 鈥渟low鈥� species (medaka) vs a 鈥渇ast鈥� species (zebrafish) with similar thermal habits, using comparative single-cell analysis. Using a combination of computational, genomic, and imaging approaches, we characterize cell type-specific differences in developmental timing after accounting for global tempo differences between these species.
