Cited by 203Neurogenesis and neuroplasticity mechanismsDevelopmental Biology and Gene RegulationNeuroscience and Neuropharmacology Research

A crucial role for Olig2 in white matter astrocyte development

Cai, Jeff, Chen, Ying, Cai, Wen-Hui, Hurlock, Edward C., Wu, Heng, Kernie, Steven G., Parada, Luis F., Lu, Q. Richard·2007·Development

Abstract

The mechanisms underlying astrocyte heterogeneity in the developing mouse brain are poorly understood. The bHLH transcription factor Olig2 is essential for motoneuron and oligodendrocyte formation; however, its role in astrocyte development remains obscure. During cortical development, Olig2 is transiently expressed in immature developing astrocytes at neonatal stages and is progressively downregulated in astrocytes at late postnatal stages. To assess the function of Olig2 in astrocyte formation, we conditionally ablated Olig2 in a spatiotemporally controlled manner. In the Olig2-ablated cortex and spinal cord, the formation of astrocytes in the white matter is severely compromised. Temporally controlled mutagenesis revealed that postnatal Olig2 function is required for astrocyte differentiation in the cerebral white matter. By contrast, astrocytes in the cortical gray matter are formed, but with sustained GFAP upregulation in the superficial layers. Cell type-specific mutagenesis and fate-mapping analyses indicate that abnormal astrocyte formation is at least in part attributable to the loss of Olig2 in developing astrocytes and their precursors. Thus, our studies uncover a crucial role for Olig2 in white matter astrocyte development and reveal divergent transcriptional requirements for, and developmental sources of, morphologically and spatially distinct astrocyte subpopulations.

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Crossref · 10.1242/dev.02847

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Authors
Cai, J., Chen, Y., Cai, W.-H., Hurlock, E. C., Wu, H., Kernie, S. G., Parada, L. F., & Lu, Q. R.
Affiliations
The University of Texas Southwestern Medical Center (US)
Corresponding author
Lu, Q. Richard
Venue
Development
Published
2007-05-15
Volume
134
Issue
10
Pages
1887-1899
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
OpenAlex
W2029606645
Cited by
203
References
48
Citations by year
2026: 9 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 13 · 2021: 17 · 2020: 11 · 2019: 13 · 2018: 7 · 2017: 4 · 2016: 10 · 2015: 13 · 2014: 16 · 2013: 14 · 2012: 12
FWCI
3.38
Type
journal article
Language
en
Open access
closed
Locations
  • Development (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
National Institute of Neurological Disorders and Stroke (R01NS050389)
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 › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
Olig2, white matter astrocytes, astrocyte development, bHLH transcription factors, conditional gene deletion, astrocyte differentiation, glial fibrillary acidic protein, astrocyte precursors, astrocyte heterogeneity, white matter, spinal cord, cortical development, fate mapping
MeSH terms
Oligodendrocyte Transcription Factor 2, Animals, Astrocytes, Brain, Cell Differentiation, Glial Fibrillary Acidic Protein, Mice, Mutant Strains, Mutation, Nerve Tissue Proteins, Spinal Cord, Developmental Biology, In Situ Hybridization, Mice, Knockout, Gene Expression Regulation, Developmental, Cell Lineage, Mice, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins

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