The nuclear orphan receptor COUP-TFI is important for differentiation of oligodendrocytes.
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.
Yamaguchi
Hideki
H
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Zhou
Cheng
C
Lin
Song-Chang
SC
Durand
Beatrice
B
Tsai
Sophia Y
SY
Tsai
Ming-Jer
MJ
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D051838:COUP Transcription Factor I; D002454:Cell Differentiation / Q000502:physiology*; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D017930:Genes, Reporter; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D050816:Octamer Transcription Factor-6; D009836:Oligodendroglia / Q000502:physiology*; D009900:Optic Nerve / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011401:Promoter Regions, Genetic; D012584:Sciatic Nerve / Q000378:metabolism / Q000648:ultrastructure; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051838:COUP Transcription Factor I; D004268:DNA-Binding Proteins; C497590:Nr2f1 protein, mouse; C494180:Pou3f1 protein, mouse; D014157:Transcription Factors; D050816:Octamer Transcription Factor-6