Abstract
Olig2, a basic helix-loop-helix (bHLH) transcription factor, is expressed in a restricted domain of the spinal cord ventricular zone that sequentially generates motoneurons and oligodendrocytes. Just prior to oligo-dendrocyte precursor formation, the domains of Olig2 and Nkx2.2 expression switch from being mutually exclusive to overlapping, and Neurogenins1 and 2 are extinguished within this region. Coexpression of Olig2 with Nkx2.2 in the spinal cord promotes ectopic and precocious oligodendrocyte differentiation. Both proteins function as transcriptional repressors in this assay. This effect is blocked by forced expression of Neurogenin1. By contrast, misexpression of Olig2 alone derepresses Neurogenins and promotes motoneuron differentiation. Olig2 therefore functions sequentially in motoneuron and oligodendrocyte fate specification. This dual action is enabled by spatio-temporal changes in the expression domains of other transcription factors with which Olig2 functionally interacts.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Base Sequence / genetics
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Basic Helix-Loop-Helix Transcription Factors
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Cell Differentiation / genetics*
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Chick Embryo
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DNA / isolation & purification
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DNA-Binding Proteins / genetics
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Gene Expression Regulation, Developmental / physiology
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Helix-Loop-Helix Motifs / genetics*
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Herpes Simplex Virus Protein Vmw65 / genetics
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High Mobility Group Proteins / genetics
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins / genetics*
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Immunohistochemistry
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In Situ Hybridization
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Molecular Sequence Data
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Myelin Basic Protein / genetics
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Nerve Tissue Proteins / genetics*
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Nuclear Proteins
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / cytology*
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Oligodendroglia / metabolism
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Receptor, Platelet-Derived Growth Factor alpha / genetics
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Recombinant Fusion Proteins / genetics
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Repressor Proteins / genetics
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SOXE Transcription Factors
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Sequence Homology, Nucleic Acid
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Spinal Cord / cytology
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Spinal Cord / embryology*
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Spinal Cord / metabolism
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Stem Cells / cytology*
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Stem Cells / metabolism
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Transcription Factors / genetics*
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Zebrafish Proteins
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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Herpes Simplex Virus Protein Vmw65
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High Mobility Group Proteins
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Homeobox Protein Nkx-2.2
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Homeodomain Proteins
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Myelin Basic Protein
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NEUROG2 protein, human
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NKX2-2 protein, human
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Nerve Tissue Proteins
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Nkx2-2 protein, mouse
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Nuclear Proteins
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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Recombinant Fusion Proteins
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Repressor Proteins
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SOXE Transcription Factors
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Sox10 protein, mouse
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Transcription Factors
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Zebrafish Proteins
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nkx2.2b protein, zebrafish
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Neurog1 protein, mouse
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DNA
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Receptor, Platelet-Derived Growth Factor alpha