胚胎中的神經(jīng)祖細(xì)胞依靠Notch效應(yīng)子基因Hes1的表達(dá),，然而,，長時間高水平的Hes1基因表達(dá)會抑制神經(jīng)祖細(xì)胞的增殖和分化,。
在4月10日的《神經(jīng)元》（Neuron）雜志上，Shimojo等人就這個問題,，用實(shí)時成像的方法發(fā)現(xiàn),，Hes1基因在神經(jīng)祖細(xì)胞中的表達(dá)呈動態(tài)振蕩的形式,。進(jìn)一步的研究證實(shí)，持續(xù)過度的Hes1基因表達(dá)會抑制基因,、Notch配體和細(xì)胞周期調(diào)節(jié)子的表達(dá),。這說明正是Hes1基因的振蕩表達(dá)決定了頸板等基因的適量表達(dá)。
令人吃驚的是,，神經(jīng)祖細(xì)胞中的頸板基因Neurogenin2（Ngn2）和Notch配體Delta-like1（Dll1）也在以振蕩的方式表達(dá)并抑制Notch信號,。通常人們認(rèn)為Notch信號可以誘導(dǎo)神經(jīng)細(xì)胞的分化，引發(fā)Hes1基因的下調(diào)以及Ngn2和Dll1基因的上調(diào),。
因此,，Shimojo等的研究結(jié)果表明，Hes1基因的振蕩表達(dá)調(diào)節(jié)著Ngn2和Dll1基因的振蕩表達(dá),。而Ngn2和Dll1基因的振蕩表達(dá)又通過引導(dǎo)Notch信號的共活化來保證神經(jīng)祖細(xì)胞的正常運(yùn)轉(zhuǎn),。（科學(xué)網(wǎng) 武彥文/編譯）
生物谷推薦原始出處：
（Neuron），Vol 58, 52-64, 10 April 2008,，Hiromi Shimojo, Ryoichiro Kageyama
Oscillations in Notch Signaling Regulate Maintenance of Neural Progenitors
Hiromi Shimojo, Toshiyuki Ohtsuka, and Ryoichiro Kageyama
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.
