Cited by 96Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationSingle-cell and spatial transcriptomics

Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics

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Sagner, Andreas, Gaber, Zachary B., Delile, Julien, Kong, Jennifer H., Rousso, David L., Pearson, Caroline A., Weicksel, Steven E., Melchionda, Manuela +3 more·2018·PLoS Biology

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Abstract

During tissue development, multipotent progenitors differentiate into specific cell types in characteristic spatial and temporal patterns. We addressed the mechanism linking progenitor identity and differentiation rate in the neural tube, where motor neuron (MN) progenitors differentiate more rapidly than other progenitors. Using single cell transcriptomics, we defined the transcriptional changes associated with the transition of neural progenitors into MNs. Reconstruction of gene expression dynamics from these data indicate a pivotal role for the MN determinant Olig2 just prior to MN differentiation. Olig2 represses expression of the Notch signaling pathway effectors Hes1 and Hes5. Olig2 repression of Hes5 appears to be direct, via a conserved regulatory element within the Hes5 locus that restricts expression from MN progenitors. These findings reveal a tight coupling between the regulatory networks that control patterning and neuronal differentiation and demonstrate how Olig2 acts as the developmental pacemaker coordinating the spatial and temporal pattern of MN generation.

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Crossref · 10.1371/journal.pbio.2003127

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Authors
Sagner, A., Gaber, Z. B., Delile, J., Kong, J. H., Rousso, D. L., Pearson, C. A., Weicksel, S. E., Melchionda, M., Mousavy Gharavy, S. N., Briscoe, J., & Novitch, B. G.
Affiliations
  • The Francis Crick Institute (GB)
  • University of California, Los Angeles (US)
  • University of Michigan (US)
Corresponding author
  • Briscoe, James
  • Novitch, Bennett G.
Venue
PLoS Biology
Published
2018-02-01
Volume
16
Issue
2
Pages
e2003127
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
OpenAlex
W2952682383
Cited by
96
References
102
Citations by year
2026: 10 · 2025: 13 · 2024: 7 · 2023: 13 · 2022: 14 · 2021: 12 · 2020: 11 · 2019: 9 · 2018: 6 · 2017: 1
FWCI
3.50
Type
journal article
Language
en
Open access
Locations
  • PLoS Biology (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
  • Research Explorer (The University of Manchester) (submittedVersion, other-oa)
Funders
  • Howard Hughes Medical Institute
  • March of Dimes Foundation
  • Wellcome Trust (FC001-051, 098325/Z/12/Z, WT098326MA)
  • Francis Crick Institute (10051)
  • Cancer Research UK (FC001-051)
  • European Commission (624973)
  • Medical Research Council (FC001051)
  • National Institute of Neurological Disorders and Stroke (R01NS089817, R01NS053976, R01NS072804, R01NS085227)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
Keywords
Olig2, Hes1, Hes5, motor neuron differentiation, motor neuron progenitors, Notch signaling, transcriptional repression, neural tube, gene regulatory networks, developmental timing, single-cell transcriptomics
MeSH terms
Transcription Factor HES-1, Oligodendrocyte Transcription Factor 2, Animals, Cell Cycle, Fluorescent Dyes, Gene Expression Regulation, Interneurons, Mice, Transgenic, Motor Neurons, Regulatory Sequences, Nucleic Acid, Repressor Proteins, Signal Transduction, Genes, Reporter, Basic Helix-Loop-Helix Proteins, Receptors, Notch, Neurogenesis, Single-Cell Analysis, Transcriptome

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