The transcription factor NFIA controls the onset of gliogenesis in the developing spinal cord
Open accessAbstract
The mechanisms controlling the transition from neurogenesis to gliogenesis in the vertebrate CNS are incompletely understood. We identified a family of transcription factors, called NFI genes, which are induced throughout the spinal cord ventricular zone (VZ) concomitantly with the induction of GLAST, an early marker of gliogenesis. NFIA is both necessary and sufficient for GLAST induction in the VZ. Unexpectedly, NFIA is also essential for the continued inhibition of neurogenesis in VZ progenitors. This function is mediated by the requirement of NFIA for the expression of HES5, a Notch effector. However, Notch effectors are unable to promote glial-fate specification in the absence of NFIA. Thus, NFIA links the abrogation of neurogenesis to a generic program of gliogenesis, in both astrocyte and oligodendrocyte VZ progenitors. At later stages, NFIA promotes migration and differentiation of astrocyte precursors, a function that is antagonized in oligodendrocyte precursors by Olig2.
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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 Deneen et al., 2006
Nfia/b are induced in MNs at later timepoints.
“Nfia/b are induced in MNs at later timepoints (Deneen et al., 2006; Kang et al., 2012).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Deneen et al., 2006
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 Deneen et al., 2006
Forced expression of Sox9 and Nfia/b does not repress neurogenesis, and neurons continue to be produced for a considerable period after their expression commences.
“However, the forced expression of these TFs does not repress neurogenesis, and neurons continue to be produced for a considerable period after their expression commences (Deneen et al., 2006).”
From Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord (2019) · cites this paper as Deneen et al., 2006
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 Deneen et al., 2006
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Self-citationmiR-219 Cooperates with miR-338 in Myelination and Promotes Myelin Repair in the CNS
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- Authors
- Deneen, B., Ho, R., Lukaszewicz, A., Hochstim, C. J., Gronostajski, R. M., & Anderson, D. J.
- Affiliations
- California Institute of Technology (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Anderson, David J.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 52
- Issue
- 6
- Pages
- 953-968
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2051655214
- Cited by
- 514
- References
- 76
- Citations by year
- 2026: 24 · 2025: 26 · 2024: 35 · 2023: 24 · 2022: 35 · 2021: 45 · 2020: 35 · 2019: 28 · 2018: 30 · 2017: 25 · 2016: 21 · 2015: 18 · 2014: 26 · 2013: 25 · 2012: 22
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2420 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- National Institutes of Health (1f32ns048666-01a2)
- National Institute of Neurological Disorders and Stroke (1F32NS048666, R01-NS23476, R01NS023476)
- 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
- NFIA, NFI transcription factors, gliogenesis, neurogenesis, GLAST, Hes5, Notch signaling, astrocyte precursors, oligodendrocyte precursor cells, Olig2, central nervous system development
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Animals, Bromodeoxyuridine, Cell Differentiation, Chick Embryo, Embryo, Mammalian, Glial Fibrillary Acidic Protein, Immunohistochemistry, Models, Biological, Nerve Tissue Proteins, Neuroglia, Spinal Cord, Stem Cells, Blotting, Western, In Situ Hybridization, Fluorescence, Gene Expression Regulation, Developmental, Excitatory Amino Acid Transporter 1, Animals, Genetically Modified, RNA Interference, Organogenesis, Microarray Analysis, Green Fluorescent Proteins, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, NFI Transcription Factors, Receptors, Notch
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