The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuron. 2010 Nov 4;68(3):442-55. doi: 10.1016/j.neuron.2010.09.028.
Regulation of progenitor cell fate determines the numbers of neurons in the developing brain. While proliferation of neural progenitors predominates during early central nervous system (CNS) development, progenitor cell fate shifts toward differentiation as CNS circuits develop, suggesting that signals from developing circuits may regulate proliferation and differentiation. We tested whether activity regulates neurogenesis in vivo in the developing visual system of Xenopus tadpoles. Both cell proliferation and the number of musashi1-immunoreactive progenitors in the optic tectum decrease as visual system connections become stronger. Visual deprivation for 2 days increased proliferation of musashi1-immunoreactive radial glial progenitors, while visual experience increased neuronal differentiation. Morpholino-mediated knockdown and overexpression of musashi1 indicate that musashi1 is necessary and sufficient for neural progenitor proliferation in the CNS. These data demonstrate a mechanism by which increased brain activity in developing circuits decreases cell proliferation and increases neuronal differentiation through the downregulation of musashi1 in response to circuit activity.
祖细胞命运的调节决定了发育中大脑中的神经元数量。虽然神经祖细胞的增殖在中枢神经系统（CNS）早期发育中占主导地位，但随着 CNS 回路的发育，祖细胞命运向分化转变，这表明来自发育中的回路的信号可能调节增殖和分化。我们测试了在非洲爪蟾蝌蚪的发育视觉系统中，活动是否调节体内的神经发生。随着视觉系统连接的增强，视神经束中的细胞增殖和 Musashi1 免疫反应性祖细胞数量减少。剥夺视觉 2 天会增加 Musashi1 免疫反应性放射状胶质祖细胞的增殖，而视觉经验会增加神经元分化。通过 morpholino 介导的 knockdown 和过表达 Musashi1 表明，Musashi1 对于 CNS 中的神经前体细胞增殖是必要和充分的。这些数据表明，通过响应回路活动下调 Musashi1，发育中的回路中增加的脑活动减少细胞增殖并增加神经元分化的机制。
