Erk1/2 promotes proliferation and inhibits neuronal differentiation of neural stem cells |
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Authors: | Bin Wang Yuan Gao Zhifeng Xiao Bing Chen Jin Han Jing Zhang Xia Wang Jianwu Dai |
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Institution: | 1. Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100190, China;2. The Graduate School, Chinese Academy of Sciences, Beijing 100190, China |
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Abstract: | 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. |
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Keywords: | Neural stem cells Proliferation Differentiation Development Signal |
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