Associate Professor University of Washington, Washington, United States
High-throughput single cell genomics now allows for comprehensive mapping of whole vertebrate organisms at unprecedented scale. However, our understanding of the effects of perturbations to development have been challenging to capture and integrate with existing atlas datasets. Here, we present a new experimental and analytical approach for high-resolution phenotyping of thousands of individually barcoded, whole zebrafish embryos in response to genetic perturbations at multiple stages of development. Using this approach, we (i) comprehensively map the zebrafish developmental landscape from 18 to 96 hours post-fertilization, (ii) statistically assess the effects of 22 genetic perturbations across ~100 cell types and 5 timepoints in a single experiment, (iii) identify a transcriptional program that sheds light on the origin of head cartilage in vertebrates, and (iv) resolve developmental trajectories and define new lineage-specific markers for rare cell populations in the peripheral nervous system. We anticipate that this dataset and workflow will expand the genetic screening capabilities in zebrafish and other organisms and catalyze mechanistic insights for many models of genetic diseases.
