Abstract
Studies have indicated that oligodendrocytes in the spinal cord originate from a ventral progenitor domain defined by expression of the oligodendrocyte-determining bHLH proteins Olig1 and Olig2. Here, we provide evidence that progenitors in the dorsal spinal cord and hindbrain also produce oligodendrocytes and that the specification of these cells may result from a dorsal evasion of BMP signaling over time. Moreover, we show that the generation of ventral oligodendrocytes in the spinal cord depends on Nkx6.1 and Nkx6.2 function, while these homeodomain proteins in the anterior hindbrain instead suppress oligodendrocyte specification. The opposing roles for Nkx6 proteins in the spinal cord and hindbrain, in turn, appear to reflect that oligodendrocytes are produced by distinct ventral progenitor domains at these axial levels. Based on these findings, we propose that oligodendrocytes derive from several distinct positional origins and that the activation of Olig1/2 at different positions is controlled by distinct genetic programs.
Publication types
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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
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Biomarkers
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins / antagonists & inhibitors
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Bone Morphogenetic Proteins / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / genetics*
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Cells, Cultured
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DNA-Binding Proteins / genetics
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Gene Expression Regulation, Developmental / genetics
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Hedgehog Proteins
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Mice
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Mice, Knockout
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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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PAX7 Transcription Factor
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Receptor, Platelet-Derived Growth Factor alpha / metabolism
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Rhombencephalon / cytology
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Rhombencephalon / embryology*
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Rhombencephalon / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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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 / drug effects
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Stem Cells / metabolism*
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transforming Growth Factor beta / antagonists & inhibitors
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Transforming Growth Factor beta / metabolism
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Biomarkers
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Bone Morphogenetic Protein 7
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Bone Morphogenetic Proteins
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DNA-Binding Proteins
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Hedgehog Proteins
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Homeodomain Proteins
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Nerve Tissue Proteins
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Nkx6-1 protein, mouse
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Nkx6.2 protein, vertebrate
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Olig1 protein, mouse
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Olig2 protein, mouse
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Oligodendrocyte Transcription Factor 2
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PAX7 Transcription Factor
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Pax7 protein, mouse
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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Receptor, Platelet-Derived Growth Factor alpha