A crucial role for Olig2 in white matter astrocyte development

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

Research output: Contribution to journalArticle

108 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1887-1899
Number of pages13
JournalDevelopment
Volume134
Issue number10
DOIs
StatePublished - May 2007

Fingerprint

Astrocytes
Mutagenesis
White Matter
Basic Helix-Loop-Helix Transcription Factors
Oligodendroglia
Motor Neurons
Spinal Cord
Up-Regulation
Down-Regulation

Keywords

  • Astrocyte differentiation and heterogeneity
  • bHLH transcription factors
  • Cortex
  • Mouse
  • Olig2
  • Oligodendrocyte lineage
  • Spatiotemporally specific knockout

ASJC Scopus subject areas

  • Anatomy
  • Cell Biology

Cite this

Cai, J., Chen, Y., Cai, W. H., Hurlock, E. C., Wu, H., Kernie, S. G., ... Lu, Q. R. (2007). A crucial role for Olig2 in white matter astrocyte development. Development, 134(10), 1887-1899. https://doi.org/10.1242/dev.02847

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.

In: Development, Vol. 134, No. 10, 05.2007, p. 1887-1899.

Research output: Contribution to journalArticle

Cai, J, Chen, Y, Cai, WH, Hurlock, EC, Wu, H, Kernie, SG, Parada, LF & Lu, QR 2007, 'A crucial role for Olig2 in white matter astrocyte development', Development, vol. 134, no. 10, pp. 1887-1899. https://doi.org/10.1242/dev.02847
Cai J, Chen Y, Cai WH, Hurlock EC, Wu H, Kernie SG et al. A crucial role for Olig2 in white matter astrocyte development. Development. 2007 May;134(10):1887-1899. https://doi.org/10.1242/dev.02847
Cai, Jeff ; Chen, Ying ; Cai, Wen Hui ; Hurlock, Edward C. ; Wu, Heng ; Kernie, Steven G. ; Parada, Luis F. ; Lu, Q. Richard. / A crucial role for Olig2 in white matter astrocyte development. In: Development. 2007 ; Vol. 134, No. 10. pp. 1887-1899.
@article{89db94fab09c4f4dbc1f6bff4b51e8ad,
title = "A crucial role for Olig2 in white matter astrocyte 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.",
keywords = "Astrocyte differentiation and heterogeneity, bHLH transcription factors, Cortex, Mouse, Olig2, Oligodendrocyte lineage, Spatiotemporally specific knockout",
author = "Jeff Cai and Ying Chen and Cai, {Wen Hui} and Hurlock, {Edward C.} and Heng Wu and Kernie, {Steven G.} and Parada, {Luis F.} and Lu, {Q. Richard}",
year = "2007",
month = "5",
doi = "10.1242/dev.02847",
language = "English (US)",
volume = "134",
pages = "1887--1899",
journal = "Development (Cambridge)",
issn = "0950-1991",
publisher = "Company of Biologists Ltd",
number = "10",

}

TY - JOUR

T1 - A crucial role for Olig2 in white matter astrocyte development

AU - Cai, Jeff

AU - Chen, Ying

AU - Cai, Wen Hui

AU - Hurlock, Edward C.

AU - Wu, Heng

AU - Kernie, Steven G.

AU - Parada, Luis F.

AU - Lu, Q. Richard

PY - 2007/5

Y1 - 2007/5

N2 - 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.

AB - 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.

KW - Astrocyte differentiation and heterogeneity

KW - bHLH transcription factors

KW - Cortex

KW - Mouse

KW - Olig2

KW - Oligodendrocyte lineage

KW - Spatiotemporally specific knockout

UR - http://www.scopus.com/inward/record.url?scp=34250618272&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34250618272&partnerID=8YFLogxK

U2 - 10.1242/dev.02847

DO - 10.1242/dev.02847

M3 - Article

C2 - 17428828

AN - SCOPUS:34250618272

VL - 134

SP - 1887

EP - 1899

JO - Development (Cambridge)

JF - Development (Cambridge)

SN - 0950-1991

IS - 10

ER -