Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Mol Cell Neurosci. 2010 Sep;45(1):26-36. doi: 10.1016/j.mcn.2010.05.006. Epub 2010 May 25.
The intermediate filament (IF) protein nestin is a widely accepted molecular marker for neural progenitor cells (NPCs), but its function during neurogenesis remains largely unknown. We found that in embryonic cortical NPCs down-regulation of the expression of nestin, but not its co-polymer IF protein vimentin, resulted in a G1 cell-cycle arrest and a severe reduction in the generation of neurons. Furthermore, down-regulating nestin expression in cultured cortical NPCs markedly suppressed their colony-formation ability and blocked the elevation of the cyclin D1/E protein level in response to the treatment with bFGF. Interestingly, nestin down-regulation caused a marked suppression in the activation of the phosphoinositide 3-kinase (PI3K) pathway but not the mitogen-activated protein kinase (MAPK) pathway in these NPCs. Moreover, defects in the proliferation of cortical NPCs caused by nestin down-regulation could be prevented by up-regulating PI3K activity. Thus, nestin is essential for the proliferation of NPCs by promoting the activation of PI3K in response to mitogenic growth factors.
中间丝（IF）蛋白巢蛋白是神经祖细胞（NPC）的广泛认可的分子标志物，但它在神经发生过程中的功能仍知之甚少。我们发现，在胚胎皮质 NPC 中，下调巢蛋白的表达，而不是其共聚物 IF 蛋白波形蛋白，会导致 G1 细胞周期停滞，并严重减少神经元的生成。此外，下调培养的皮质 NPC 中的巢蛋白表达显著抑制了它们的集落形成能力，并阻断了 bFGF 处理后细胞周期蛋白 D1/E 蛋白水平的升高。有趣的是，巢蛋白下调导致 NPC 中磷酸肌醇 3-激酶（PI3K）途径的激活明显受到抑制，而丝裂原活化蛋白激酶（MAPK）途径不受抑制。此外，通过上调 PI3K 活性，可以预防由巢蛋白下调引起的皮质 NPC 增殖缺陷。因此，巢蛋白通过促进有丝分裂生长因子刺激的 PI3K 激活对于 NPC 的增殖是必需的。
