Neuron：神经祖细胞Notch信号调节
胚胎中的神经祖细胞依靠Notch效应子基因Hes1的表达，然而，长时间高水平的Hes1基因表达会抑制神经祖细胞的增殖和分化。
在4月10日的《神经元》（Neuron）杂志上，Shimojo等人就这个问题，用实时成像的方法发现，Hes1基因在神经祖细胞中的表达呈动态振荡的形式。进一步的研究证实，持续过度的Hes1基因表达会抑制基因、Notch配体和细胞周期调节子的表达。这说明正是Hes1基因的振荡表达决定了颈板等基因的适量表达。
令人吃惊的是，神经祖细胞中的颈板基因Neurogenin2（Ngn2）和Notch配体Delta-like1（Dll1）也在以振荡的方式表达并抑制Notch信号。通常人们认为Notch信号可以诱导神经细胞的分化，引发Hes1基因的下调以及Ngn2和Dll1基因的上调。
因此，Shimojo等的研究结果表明，Hes1基因的振荡表达调节着Ngn2和Dll1基因的振荡表达。而Ngn2和Dll1基因的振荡表达又通过引导Notch信号的共活化来保证神经祖细胞的正常运转。（科学网 武彦文/编译）
生物谷推荐原始出处：
（Neuron），Vol 58, 52-64, 10 April 2008，Hiromi Shimojo, Ryoichiro Kageyama
Oscillations in Notch Signaling Regulate Maintenance of Neural Progenitors
Expression of the Notch effector gene Hes1 is required for maintenance of neural progenitors in the embryonic brain, but persistent and high levels of Hes1 expression inhibit proliferation and differentiation of these cells. Here, by using a real-time imaging method, we found that Hes1 expression dynamically oscillates in neural progenitors. Furthermore, sustained overexpression of Hes1 downregulates expression of proneural genes, Notch ligands, and cell cycle regulators, suggesting that their proper expression depends on Hes1 oscillation. Surprisingly, the proneural gene Neurogenin2 (Ngn2) and the Notch ligand Delta-like1 (Dll1) are also expressed in an oscillatory manner by neural progenitors, and inhibition of Notch signaling, a condition known to induce neuronal differentiation, leads to downregulation of Hes1 and sustained upregulation of Ngn2 and Dll1. These results suggest that Hes1 oscillation regulates Ngn2 and Dll1 oscillations, which in turn lead to maintenance of neural progenitors by mutual activation of Notch signaling.
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