Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics
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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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Available single cell expression profiling studies of neural development have either focussed on in vitro-derived neural progenitor cells or analysed cells from postnatal animals or late-stage embryos.
“available single cell expression profiling studies of neural development have either focussed on in vitro-derived neural progenitor cells (Briggs et al., 2017; Sagner et al., 2018), or analysed cells from postnatal animals or late-stage embryos”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Sagner et al., 2018
Upregulation of Olig2 coincides with Neurog2 expression and neurogenesis in MN progenitors.
“In line with this, we have recently demonstrated that upregulation of Olig2 coincides with Neurog2 expression and neurogenesis in MN progenitors (Sagner et al., 2018).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Sagner et al., 2018
Upregulation of Olig2 precedes MN formation in vivo and in vitro.
“We have previously demonstrated that upregulation of Olig2 precedes MN formation in vivo and in vitro (Sagner et al., 2018).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Sagner et al., 2018
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microRNAs control temporal patterning of the vertebrate nervous systemPreprint
Renaux, E., Caudet-Segarra, L., Mistry, A. S., Pandey, M., Sagner, J., Jäck, H., Wittmann, J., Wegner, M., & Sagner, A. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.10.02.755877
- 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.
- ORCID
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-02-01
- Volume
- 16
- Issue
- 2
- Pages
- e2003127
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC5811045
- 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
- Update notices
- new_version (2018-02-13)
- Open access
- gold
- doi.org
- Licence
- 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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