Sox9 and NFIA coordinate a transcriptional regulatory cascade during the initiation of gliogenesis
Open accessAbstract
Transcriptional cascades that operate over the course of lineage development are fundamental mechanisms that control cellular differentiation. In the developing central nervous system (CNS), these mechanisms are well characterized during neurogenesis, but remain poorly defined during neural stem cell commitment to the glial lineage. NFIA is a transcription factor that plays a crucial role in the onset of gliogenesis; we found that its induction is regulated by the transcription factor Sox9 and that this relationship mediates the initiation of gliogenesis. Subsequently, Sox9 and NFIA form a complex and coregulate a set of genes induced after glial initiation. Functional studies revealed that a subset of these genes, Apcdd1 and Mmd2, perform key migratory and metabolic roles during astro-gliogenesis, respectively. In sum, these studies delineate a transcriptional regulatory cascade that operates during the initiation of gliogenesis and identifies a unique set of genes that regulate key aspects of astro-glial precursor physiology during development.
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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 Kang et al., 2012
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 Kang et al., 2012
The authors observed expression of FGF ligands in multiple neuronal subtypes, whereas neural progenitors at later stages upregulated Fgfr3 and Fgfbp3.
“Lastly, we observed the expression of FGF ligands in multiple neuronal subtypes, whereas neural progenitors at later stages upregulated FGF receptor3 (Fgfr3) and FGF-binding protein 3 (Fgfbp3) (Gonzalez-Quevedo et al., 2010; 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 Kang et al., 2012
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 Kang et al., 2012
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 Kang et al., 2012
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References 64 · Cited by 373
- Authors
- Kang, P., Lee, H. K., Glasgow, S. M., Finley, M., Donti, T., Gaber, Z. B., Graham, B. H., Foster, A. E., Novitch, B. G., Gronostajski, R. M., & Deneen, B.
- Affiliations
- Baylor College of Medicine (US)
- University of California, Los Angeles (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Deneen, Benjamin
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-04
- Volume
- 74
- Issue
- 1
- Pages
- 79-94
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3543821
- OpenAlex
- W2072182588
- Cited by
- 373
- References
- 64
- Citations by year
- 2026: 21 · 2025: 37 · 2024: 33 · 2023: 32 · 2022: 37 · 2021: 34 · 2020: 32 · 2019: 30 · 2018: 23 · 2017: 21 · 2016: 17 · 2015: 16 · 2014: 17 · 2013: 17 · 2012: 5
- FWCI
- 5.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (5-T32HL092332-08, T32HL092332)
- National Institute of Neurological Disorders and Stroke (R01NS053976, R01NS072804, R01NS071153)
- 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, NFIA, gliogenesis, neural stem cell differentiation, APCDD1, astrocyte migration, astrocyte metabolism, central nervous system development
- MeSH terms
- Animals, Cell Differentiation, Central Nervous System, Chick Embryo, Humans, Membrane Proteins, Neuroglia, Stem Cells, Transcription, Genetic, Gene Expression Regulation, Developmental, Cell Lineage, Organogenesis, Intracellular Signaling Peptides and Proteins, Mice, NFI Transcription Factors, SOX9 Transcription Factor
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