Ohtsuka T, Ishibashi M, Gradwohl G, Nakanishi S, Guillemot F, Kageyama R
Institute for Virus Research, Kyoto University, Shogoin-Kawahara, Sakyo-ku, Kyoto 606-8507, USA.
EMBO J. 1999 Apr 15;18(8):2196-207. doi: 10.1093/emboj/18.8.2196.
While the transmembrane protein Notch plays an important role in various aspects of development, and diseases including tumors and neurological disorders, the intracellular pathway of mammalian Notch remains very elusive. To understand the intracellular pathway of mammalian Notch, the role of the bHLH genes Hes1 and Hes5 (mammalian hairy and Enhancer-of-split homologues) was examined by retrovirally misexpressing the constitutively active form of Notch (caNotch) in neural precursor cells prepared from wild-type, Hes1-null, Hes5-null and Hes1-Hes5 double-null mouse embryos. We found that caNotch, which induced the endogenous Hes1 and Hes5 expression, inhibited neuronal differentiation in the wild-type, Hes1-null and Hes5-null background, but not in the Hes1-Hes5 double-null background. These results demonstrate that Hes1 and Hes5 are essential Notch effectors in regulation of mammalian neuronal differentiation.
虽然跨膜蛋白Notch在发育的各个方面以及包括肿瘤和神经疾病在内的多种疾病中发挥着重要作用，但哺乳动物Notch的细胞内信号通路仍然非常难以捉摸。为了了解哺乳动物Notch的细胞内信号通路，我们通过逆转录病毒在从野生型、Hes1基因敲除、Hes5基因敲除以及Hes1-Hes5双基因敲除小鼠胚胎制备的神经前体细胞中错误表达组成型激活形式的Notch（caNotch），来研究bHLH基因Hes1和Hes5（哺乳动物毛状和分裂增强子同源物）的作用。我们发现，能诱导内源性Hes1和Hes5表达的caNotch在野生型、Hes1基因敲除和Hes5基因敲除背景下抑制神经元分化，但在Hes1-Hes5双基因敲除背景下则不然。这些结果表明，Hes1和Hes5是调节哺乳动物神经元分化的关键Notch效应器。
