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Emergence of neuronal diversity during vertebrate brain development

View ORCID ProfileBushra Raj, View ORCID ProfileJeffrey A. Farrell, View ORCID ProfileAaron McKenna, Jessica L. Leslie, View ORCID ProfileAlexander F. Schier
doi: https://doi.org/10.1101/839860
Bushra Raj
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
2Allen Discovery Center for Cell Lineage Tracing, Seattle, Washington, USA
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  • For correspondence: bushranraj@gmail.com schier@mcb.harvard.edu
Jeffrey A. Farrell
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
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Aaron McKenna
3Department of Molecular and Systems Biology, Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA
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Jessica L. Leslie
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
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Alexander F. Schier
1Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts, USA
2Allen Discovery Center for Cell Lineage Tracing, Seattle, Washington, USA
4Biozentrum, University of Basel, Switzerland
5Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
6Harvard Stem Cell Institute, Harvard University, Cambridge, Massachusetts, USA
7Center for Brain Science, Harvard University, Cambridge, Massachusetts, USA
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  • ORCID record for Alexander F. Schier
  • For correspondence: bushranraj@gmail.com schier@mcb.harvard.edu
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ABSTRACT

Neurogenesis in the vertebrate brain comprises many steps ranging from the proliferation of progenitors to the differentiation and maturation of neurons. Although these processes are highly regulated, the landscape of transcriptional changes and progenitor identities underlying brain development are poorly characterized. Here, we describe the first developmental single-cell RNA-seq catalog of more than 200,000 zebrafish brain cells encompassing 12 stages from 12 hours post-fertilization to 15 days post-fertilization. We characterize known and novel gene markers for more than 800 clusters across these timepoints. Our results capture the temporal dynamics of multiple neurogenic waves from embryo to larva that expand neuronal diversity from ∼20 cell types at 12 hpf to ∼100 cell types at 15 dpf. We find that most embryonic neural progenitor states are transient and transcriptionally distinct from long-lasting neural progenitors of post-embryonic stages. Furthermore, we reconstruct cell specification trajectories for the retina and hypothalamus, and identify gene expression cascades and novel markers. Our analysis reveal that late-stage retinal neural progenitors transcriptionally overlap cell states observed in the embryo, while hypothalamic neural progenitors become progressively distinct with developmental time. These data provide the first comprehensive single-cell transcriptomic time course for vertebrate brain development and suggest distinct neurogenic regulatory paradigms between different stages and tissues.

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Posted November 12, 2019.
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Emergence of neuronal diversity during vertebrate brain development
Bushra Raj, Jeffrey A. Farrell, Aaron McKenna, Jessica L. Leslie, Alexander F. Schier
bioRxiv 839860; doi: https://doi.org/10.1101/839860
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Emergence of neuronal diversity during vertebrate brain development
Bushra Raj, Jeffrey A. Farrell, Aaron McKenna, Jessica L. Leslie, Alexander F. Schier
bioRxiv 839860; doi: https://doi.org/10.1101/839860

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