ABSTRACT
Zebrafish, a popular organism for studying embryonic development and for modeling human diseases, has so far lacked a systematic functional annotation program akin to those in other animal models. To address this, we formed the international DANIO-CODE consortium and created a central repository to store and process zebrafish developmental functional genomic data. Our data coordination center ( https://danio-code.zfin.org ) combines a total of 1,802 sets of unpublished and re-analyzed published genomic data, which we used to improve existing annotations and show its utility in experimental design. We identified over 140,000 cis-regulatory elements throughout development, including classes with distinct features dependent on their activity in time and space. We delineated the distinct distance topology and chromatin features between regulatory elements active during zygotic genome activation and those active during organogenesis. Finally, we matched regulatory elements and epigenomic landscapes between zebrafish and mouse and predicted functional relationships between them beyond sequence similarity, thus extending the utility of zebrafish developmental genomics to mammals.
Subject(s)
Databases, Genetic , Gene Expression Regulation, Developmental , Genome , Genomics , Regulatory Sequences, Nucleic Acid , Zebrafish Proteins , Zebrafish , Animals , Chromatin/genetics , Genome/genetics , Humans , Mice , Molecular Sequence Annotation , Organogenesis/genetics , Regulatory Sequences, Nucleic Acid/genetics , Zebrafish/embryology , Zebrafish/genetics , Zebrafish Proteins/geneticsABSTRACT
Neurogenesis comprises many highly regulated processes including proliferation, differentiation, and maturation. However, the transcriptional landscapes underlying brain development are poorly characterized. We describe a developmental single-cell catalog of â¼220,000 zebrafish brain cells encompassing 12 stages from embryo to larva. We characterize known and novel gene markers for â¼800 clusters and provide an overview of the diversification of neurons and progenitors across these time points. We also introduce an optimized GESTALT lineage recorder that enables higher expression and recovery of Cas9-edited barcodes to query lineage segregation. Cell type characterization indicates that most embryonic neural progenitor states are transitory and transcriptionally distinct from neural progenitors of post-embryonic stages. Reconstruction of cell specification trajectories reveals that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo. The zebrafish brain development atlas provides a resource to define and manipulate specific subsets of neurons and to uncover the molecular mechanisms underlying vertebrate neurogenesis.
