The Sox9 transcription factor determines glial fate choice in the developing spinal cord
Open accessAbstract
The mechanism that causes neural stem cells in the central nervous system to switch from neurogenesis to gliogenesis is poorly understood. Here we analyzed spinal cord development of mice in which the transcription factor Sox9 was specifically ablated from neural stem cells by the CRE/loxP recombination system. These mice exhibit defects in the specification of oligodendrocytes and astrocytes, the two main types of glial cells in the central nervous system. Accompanying an early dramatic reduction in progenitors of the myelin-forming oligodendrocytes, there was a transient increase in motoneurons. Oligodendrocyte progenitor numbers recovered at later stages of development, probably owing to compensatory actions of the related Sox10 and Sox8, both of which overlap with Sox9 in the oligodendrocyte lineage. In agreement, compound loss of Sox9 and Sox10 led to a further decrease in oligodendrocyte progenitors. Astrocyte numbers were also severely reduced in the absence of Sox9 and did not recover at later stages of spinal cord development. Taking the common origin of motoneurons and oligodendrocytes as well as V2 interneurons and some astrocytes into account, stem cells apparently fail to switch from neurogenesis to gliogenesis in at least two domains of the ventricular zone, indicating that Sox9 is a major molecular component of the neuron-glia switch in the developing spinal cord.
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Following neurogenesis, which lasts until approximately e13 in mouse, remaining undifferentiated progenitors in the neural tube produce glia cells, accompanied by specific changes in gene expression in progenitors.
“Following the period of neurogenesis, which lasts until ∼e13 in mouse, the remaining undifferentiated progenitors in the neural tube produce glia cells. This is accompanied by specific changes in gene expression in progenitors”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Stolt et al., 2003
In the spinal cord, a transcriptional cascade of Sox9 and Nfia/b in progenitors underlies the progressive activation of gliogenesis.
“In the spinal cord, a transcriptional cascade of Sox9 and Nfia/b in progenitors underlies the progressive activation of gliogenesis (Deneen et al., 2006; Kang et al., 2012; Stolt et al., 2003).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Stolt et al., 2003
Sox9 expression begins between e9.5 and e10.5, whereas Nfia/b is expressed from e11.5.
“Sox9 expression begins between e9.5 and e10.5, whereas Nfia/b is expressed from e11.5 (Deneen et al., 2006; Stolt et al., 2003).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Stolt et al., 2003
The onset of expression of Sox9 coincides with the switch of V1 neurons from Renshaw cells (onecut-expressing) to Foxp2-expressing neurons.
“The onset of expression of Sox9 coincides with the switch of V1 neurons from Renshaw cells (onecut-expressing) to Foxp2-expressing neurons (Kang et al., 2012; Stam et al., 2012; Stolt et al., 2003).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Stolt et al., 2003
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References 36 · Cited by 636
- Authors
- Stolt, C. C., Lommes, P., Sock, E., Chaboissier, M.-C., Schedl, A., & Wegner, M.
- Affiliations
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- Inserm (FR)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2003-07-01
- Volume
- 17
- Issue
- 13
- Pages
- 1677-1689
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC196138
- OpenAlex
- W2138192079
- Cited by
- 636
- References
- 36
- Citations by year
- 2026: 23 · 2025: 20 · 2024: 28 · 2023: 31 · 2022: 27 · 2021: 33 · 2020: 35 · 2019: 25 · 2018: 21 · 2017: 28 · 2016: 25 · 2015: 23 · 2014: 27 · 2013: 47 · 2012: 25
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Keywords
- SOX9, spinal cord development, oligodendrocyte progenitors, astrocytes, motor neurons, SOX10, Sox8, neural stem cells, ventricular zone, myelination
- MeSH terms
- Animals, Astrocytes, Cell Count, Central Nervous System, High Mobility Group Proteins, Interneurons, Mice, Transgenic, Motor Neurons, Oligodendroglia, Recombination, Genetic, Spinal Cord, Stem Cells, Transcription Factors, Mice, SOX9 Transcription Factor
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