Yamaguchi Hideki, Zhou Cheng, Lin Song-Chang, Durand Beatrice, Tsai Sophia Y, Tsai Ming-Jer
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Dev Biol. 2004 Feb 15;266(2):238-51. doi: 10.1016/j.ydbio.2003.10.038.
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.
我们在此报告，核激素受体超家族的一个成员，鸡卵清蛋白上游启动子转录因子1（COUP-TFI），在神经胶质细胞发育及随后的中枢神经系统髓鞘形成中起关键作用。我们证明COUP-TF1在少突胶质细胞谱系的细胞中表达。此外，我们证明COUP-TFI基因敲除突变小鼠在中枢神经系统中表现出轴突髓鞘形成延迟和脱髓鞘增加。通过体外分化试验，我们表明这些髓鞘形成缺陷是由于少突胶质细胞分化延迟所致。最后，原位杂交和转染分析表明，COUP-TFI作为SCIP/Oct-6/Tst-1的上游调节因子，SCIP/Oct-6/Tst-1是一种参与轴突髓鞘形成的转录因子。综上所述，这些结果表明COUP-TFI是少突胶质细胞分化的重要调节因子。
