| A crucial role for Olig2 in white matter astrocyte development. | |
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MedLine Citation:
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PMID: 17428828 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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Jeff Cai; Ying Chen; Wen-Hui Cai; Edward C Hurlock; Heng Wu; Steven G Kernie; Luis F Parada; Q Richard Lu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-04-11 |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 134 ISSN: 0950-1991 ISO Abbreviation: Development Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-05-01 Completed Date: 2007-07-20 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 1887-99 Citation Subset: IM |
Affiliation:
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Department of Developmental Biology and Kent Waldrep Foundation Center for Basic Neuroscience Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Astrocytes / cytology* Basic Helix-Loop-Helix Transcription Factors / biosynthesis*, physiology* Brain / embryology* Cell Differentiation Cell Lineage Developmental Biology Gene Expression Regulation, Developmental* Glial Fibrillary Acidic Protein / metabolism In Situ Hybridization Mice Mice, Knockout Mice, Mutant Strains Mutation Nerve Tissue Proteins / biosynthesis*, physiology* Spinal Cord / embryology |
| Grant Support | |
ID/Acronym/Agency:
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R01 NS050389/NS/NINDS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Basic Helix-Loop-Helix Transcription Factors; 0/Glial Fibrillary Acidic Protein; 0/Nerve Tissue Proteins; 0/Olig2 protein, mouse |
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