Wang Bin, Gao Yuan, Xiao Zhifeng, Chen Bing, Han Jin, Zhang Jing, Wang Xia, Dai Jianwu
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China.
Neurosci Lett. 2009 Sep 25;461(3):252-7. doi: 10.1016/j.neulet.2009.06.020. Epub 2009 Jun 17.
Neural stem cells (NSCs) are in a complex niche in which cell-extrinsic cues and cell-intrinsic genetic mechanisms in chorus mediate their cellular processes such as self-renewal and differentiation. In this study, we found that inactivation of Erk1/2 with U0126 in NSCs significantly promoted neuronal differentiation and inhibited proliferation. Sustained Erk1/2 inactivity was required in this process. We also found that nerve growth factor (NGF) and collagen could promote the proliferation and inhibit neuronal differentiation by activating phosphorylation of Erk1/2. Cell-cycle regulators such as cyclin-dependent kinase 2 (Cdk2), Cyclin D1 and Hes1 mediated the effect of Erk on NSCs proliferation and differentiation. Our results showed that Erk1/2 played an important role in the interplay between cell-extrinsic cues and cell-intrinsic genetic mechanisms in neural stem cell biology.
神经干细胞（NSCs）处于一个复杂的微环境中，在这个微环境中，细胞外信号和细胞内遗传机制共同调节其自我更新和分化等细胞过程。在本研究中，我们发现用U0126使神经干细胞中的Erk1/2失活可显著促进神经元分化并抑制增殖。在此过程中需要持续的Erk1/2失活。我们还发现神经生长因子（NGF）和胶原蛋白可通过激活Erk1/2的磷酸化来促进增殖并抑制神经元分化。细胞周期调节因子如细胞周期蛋白依赖性激酶2（Cdk2）、细胞周期蛋白D1和Hes1介导了Erk对神经干细胞增殖和分化的影响。我们的结果表明，Erk1/2在神经干细胞生物学中细胞外信号与细胞内遗传机制的相互作用中发挥着重要作用。
