Abstract
We report here that a member of the nuclear hormone receptor superfamily, chicken ovalbumin upstream promoter-transcription factor 1 (COUP-TFI), plays a critical role in glial cell development and subsequent central nervous system myelination. We demonstrate that COUP-TF1 is expressed in cells of oligodendrocyte lineage. Furthermore, we demonstrate that COUP-TFI null mutant mice exhibit delayed axon myelination and increased dysmyelination in the central nervous system. Using in vitro differentiation assays, we show that these myelination defects are due to delays in oligodendrocyte differentiation. Finally, in situ hybridization and transfection analysis suggests that COUP-TFI acts as an upstream regulator of SCIP/Oct-6/Tst-1, a transcription factor involved in axon myelination. Taken together, these results suggest that COUP-TFI is an important regulator of oligodendrocyte differentiation.
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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Brain / cytology
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Brain / metabolism
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COUP Transcription Factor I
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Cell Differentiation / physiology*
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Chickens
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation
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Genes, Reporter
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In Situ Hybridization
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Mice
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Mice, Knockout
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Myelin Sheath / metabolism*
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Myelin Sheath / pathology
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Nerve Fibers, Myelinated / metabolism
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Nerve Fibers, Myelinated / pathology
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Nerve Fibers, Myelinated / ultrastructure
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Octamer Transcription Factor-6
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Oligodendroglia / physiology*
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Optic Nerve / metabolism
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Optic Nerve / pathology
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Optic Nerve / ultrastructure
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Promoter Regions, Genetic
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Sciatic Nerve / metabolism
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Sciatic Nerve / ultrastructure
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Transcription Factors / genetics
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Transcription Factors / metabolism*
Substances
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COUP Transcription Factor I
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DNA-Binding Proteins
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Nr2f1 protein, mouse
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Pou3f1 protein, mouse
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Transcription Factors
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Octamer Transcription Factor-6