Ohtsuka T, Asahi M, Matsuura N, Kikuchi H, Hojo M, Kageyama R, Ohkubo H, Hoshimaru M
Department of Neurosurgery, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606, Japan.
Cell Tissue Res. 1998 Jul;293(1):23-9. doi: 10.1007/s004410051094.
Expression of nine neurogenic basic helix-loop-helix (bHLH) transcription factors was examined in an immortalized neuronal progenitor cell line HC2S2, which differentiates into neurons after suppression of the v-myc expression with tetracycline. Expression of MASH-1, NeuroD, NeuroD-related factor (NDRF) and HES-1 was demonstrated in HC2S2 cells by Northern blot analysis using total RNA. Expression of MASH-1 mRNA was downregulated upon differentiation of HC2S2 cells into mature neurons. In contrast, NeuroD and NDRF mRNA expression was maintained all through the differentiation. The expression of HES-1, a negative regulator of the neuronal differentiation, was upregulated temporarily in accordance with the suppression of the v-myc expression and was downregulated upon the differentiation of HC2S2 cells into neurons. The reduced expression of HES-1 mRNA in undifferentiated HC2S2 cells may be explained by the transcriptional suppression of HES-1 by the myc oncoprotein. The above data imply that both HES-1 and MASH-1 need to be downregulated at the time of accomplishment of the terminal differentiation into mature neurons and that NeuroD and NDRF participate in the regulatory process of the terminal differentiation in combination.
在永生化神经元祖细胞系HC2S2中检测了9种神经源性碱性螺旋-环-螺旋(bHLH)转录因子的表达,该细胞系在用四环素抑制v-myc表达后可分化为神经元。通过使用总RNA的Northern印迹分析,在HC2S2细胞中证实了MASH-1、NeuroD、神经D相关因子(NDRF)和HES-1的表达。当HC2S2细胞分化为成熟神经元时,MASH-1 mRNA的表达下调。相反,NeuroD和NDRF mRNA的表达在整个分化过程中保持不变。HES-1作为神经元分化的负调节因子,其表达随着v-myc表达的抑制而暂时上调,并在HC2S2细胞分化为神经元时下调。未分化的HC2S2细胞中HES-1 mRNA表达的降低可能是由于myc癌蛋白对HES-1的转录抑制所致。上述数据表明,在完成向成熟神经元的终末分化时,HES-1和MASH-1都需要下调,并且NeuroD和NDRF共同参与终末分化的调节过程。