Abstract
Within the motoneuron precursor (pMN) domain of the developing spinal cord, the bHLH transcription factor, Olig2, plays critical roles in pattern formation and the generation of motor neuron and oligodendrocyte precursors. How are the multiple functions of Olig2 regulated? We have isolated a large BAC clone encompassing the human OLIG2 locus that rescues motor neuron and oligodendrocyte development but not normal pattern formation in Olig2(-/-) embryos. Within the BAC clone, we identified a conserved 3.6 kb enhancer sub-region that directs reporter expression specifically in the motor neuron lineage but not oligodendrocyte lineage in vivo. Our findings indicate complex regulation of Olig2 by stage- and lineage-specific regulatory elements. They further suggest that transcriptional regulation of Olig2 is involved in segregation of pMN neuroblasts.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Basic Helix-Loop-Helix Transcription Factors / biosynthesis*
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Basic Helix-Loop-Helix Transcription Factors / deficiency
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Cell Differentiation / genetics
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Cell Differentiation / physiology
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Cell Lineage / genetics
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Cell Lineage / physiology*
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Chromosomes, Artificial, Bacterial
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Enhancer Elements, Genetic
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Humans
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Mice
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Mice, Knockout
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Mice, Transgenic
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Motor Neurons / cytology
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Motor Neurons / physiology*
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Nerve Tissue Proteins / biosynthesis*
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Nerve Tissue Proteins / deficiency
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Nerve Tissue Proteins / genetics
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Oligodendrocyte Transcription Factor 2
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Oligodendroglia / cytology
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Oligodendroglia / metabolism
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Spinal Cord / cytology*
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Spinal Cord / embryology*
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Stem Cells / cytology
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Stem Cells / physiology
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Nerve Tissue Proteins
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OLIG2 protein, human
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2