Oscillations in notch signaling regulate maintenance of neural progenitors
Oscillations in notch signaling regulate maintenance of neural progenitors
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DOI：
10.1016/j.neuron.2008.02.014
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发表时间：
2008-04-10
期刊：
影响因子：
16.2
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Shimojo, Hiromi;Ohtsuka, Toshiyuki;Kageyama, Ryoichiro
Notch效应基因Hes1的表达是维持胚胎脑中神经祖细胞所必需的，但Hes1的持续高水平表达抑制了这些细胞的增殖和分化。在这里，通过使用实时成像方法，我们发现Hes1表达在神经祖细胞中动态振荡。此外，Hes1的持续过表达下调原神经基因、Notch配体和细胞周期调节因子的表达，表明它们的正确表达依赖于Hes1振荡。令人惊讶的是，前神经基因神经生成素2（Ngn 2）和Notch配体Delta样1（Dill）也由神经祖细胞以振荡方式表达，并且Notch信号传导（已知诱导神经元分化的条件）的抑制导致Hes 1的下调和Ngn 2和Dill的持续上调。这些结果表明，Hes1振荡调节Ngn 2和Dill振荡，这反过来又导致通过Notch信号的相互激活来维持神经祖细胞。
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 (Dill) 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 Dill. These results suggest that Hes1 oscillation regulates Ngn2 and Dill oscillations, which in turn lead to maintenance of neural progenitors by mutual activation of Notch signaling.