Dlx1 and Dlx2 control neuronal versus oligodendroglial cell fate acquisition in the developing forebrain
Open accessAbstract
Progenitors within the ventral telencephalon can generate GABAergic neurons and oligodendrocytes, but regulation of the neuron-glial switch is poorly understood. We investigated the combinatorial expression and function of Dlx1&2, Olig2, and Mash1 transcription factors in the ventral telencephalon. We show that Dlx homeobox transcription factors, required for GABAergic interneuron production, repress oligodendrocyte precursor cell (OPC) formation by acting on a common progenitor to determine neuronal versus oligodendroglial cell fate acquisition. We demonstrate that Dlx1&2 negatively regulate Olig2-dependant OPC formation and that Mash1 promotes OPC formation by restricting the number of Dlx+ progenitors. Progenitors transplanted from Dlx1&2 mutant ventral telencephalon into newborn wild-type mice do not produce neurons but differentiate into myelinating oligodendrocytes that survive into adulthood. Our results identify another role for Dlx genes as modulators of neuron versus oligodendrocyte development in the ventral embryonic forebrain.
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OLIG2 is known to regulate progenitor self-renewal at earlier developmental stages and is a master regulator for oligodendrocyte lineage specification in the ventral telencephalon.
“This is an interesting finding given that OLIG2 is known to regulate progenitor self-renewal at earlier developmental stages and is a master regulator for oligodendrocyte lineage specification in the ventral telencephalon44,45.”
From Single-cell brain organoid screening identifies developmental defects in autism (2023) · cites this paper as [44]
Intermediate progenitor cells in the MGE and CGE are transcriptionally heterogeneous.
“intermediate progenitor cells in the MGE and CGE are transcriptionally heterogeneous”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Petryniak et al., 2007
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- Authors
- Petryniak, M. A., Potter, G. B., Rowitch, D. H., & Rubenstein, J. L. R.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Potter, Gregory B.
- Rubenstein, John L.R.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 55
- Issue
- 3
- Pages
- 417-433
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2039927
- OpenAlex
- W2031224620
- Cited by
- 371
- References
- 72
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 10 · 2023: 15 · 2022: 27 · 2021: 26 · 2020: 24 · 2019: 17 · 2018: 11 · 2017: 19 · 2016: 16 · 2015: 19 · 2014: 19 · 2013: 34 · 2012: 9
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01 MH4942801, F32MH070211, K05MH065670, R01MH049428, R37MH049428)
- National Institute of Neurological Disorders and Stroke (R01NS40511, L40 NS056772, R01NS040511)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD-07162H, T32HD007162)
- 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 › Congenital heart defects research
- Keywords
- DLX1, Dlx2, oligodendrocyte precursor cells, GABAergic interneurons, ventral telencephalon, Olig2, ASCL1, transcription factors, forebrain development, myelination
- MeSH terms
- Oligodendrocyte Transcription Factor 2, Animals, Animals, Newborn, Cell Differentiation, Cell Division, Cell Movement, Cerebral Ventricles, Myelin Basic Protein, Mutation, Nerve Tissue Proteins, Neurons, Oligodendroglia, Stem Cells, Telencephalon, Time Factors, Transcription Factors, Prosencephalon, Homeodomain Proteins, Stem Cell Transplantation, Mice, Basic Helix-Loop-Helix Proteins
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