Emergence of Neuronal Diversity during Vertebrate Brain Development

Bushra Raj; Jeffrey A Farrell; Jialin Liu; Jakob El Kholtei; Adam N Carte; Joaquin Navajas Acedo; Lucia Y Du; Aaron McKenna; Đorđe Relić; Jessica M Leslie; Alexander F Schier

doi:10.1016/j.neuron.2020.09.023

Emergence of Neuronal Diversity during Vertebrate Brain Development

Neuron. 2020 Dec 23;108(6):1058-1074.e6. doi: 10.1016/j.neuron.2020.09.023. Epub 2020 Oct 16.

Authors

Affiliations

¹ Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA. Electronic address: bushranraj@gmail.com.
² Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Unit on Cell Specification and Differentiation, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20814, USA.
³ Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA; Biozentrum, University of Basel, 4056 Basel, Switzerland.
⁴ Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Biozentrum, University of Basel, 4056 Basel, Switzerland; Systems, Synthetic, and Quantitative Biology Program, Harvard University, Cambridge, MA 02138, USA.
⁵ Department of Molecular and Systems Biology, Dartmouth Geisel School of Medicine, Lebanon, NH 03756, USA.
⁶ Biozentrum, University of Basel, 4056 Basel, Switzerland; Swiss Institute of Bioinformatics (SIB), 4056 Basel, Switzerland.
⁷ Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
⁸ Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Allen Discovery Center for Cell Lineage Tracing, Seattle, WA, USA; Biozentrum, University of Basel, 4056 Basel, Switzerland; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Harvard University, Cambridge, MA 02138, USA; Center for Brain Science, Harvard University, Cambridge, MA 02138, USA. Electronic address: alex.schier@unibas.ch.

Abstract

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 ∼220,000 zebrafish brain cells encompassing 12 stages from embryo to larva. We characterize known and novel gene markers for ∼800 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.

Keywords: CRISPR-Cas9 barcoding; brain; cell specification; lineage; neurogenesis; progenitor; retina; scRNA-Seq; transcriptional cascade; zebrafish.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Brain / cytology
Brain / growth & development*
Cell Differentiation / physiology
Cell Lineage / physiology*
Gene Expression Regulation, Developmental
Neurogenesis / physiology*
Neurons / cytology*
Zebrafish / genetics*

Abstract

Publication types

MeSH terms

Grants and funding