Axin Directs the Amplification and Differentiation of Intermediate Progenitors in the Developing Cerebral Cortex
Axin Directs the Amplification and Differentiation of Intermediate Progenitors in the Developing Cerebral Cortex
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DOI：
10.1016/j.neuron.2013.06.017
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发表时间：
2013-08-21
期刊：
影响因子：
16.2
通讯作者：
Ip, Nancy Y.
中科院分区：
文献类型：
--
作者：
Fang, Wei-Qun;Chen, Wei-Wei;Ip, Nancy Y.
哺乳动物大脑皮层的扩张是由中间祖细胞（IPs）的扩增和神经元分化之间的协调平衡所保护的。尽管如此，控制这些过程的分子控制仍不清楚。我们发现，在发育中的大脑皮层中，支架蛋白轴蛋白是决定IP群体大小和最终神经元数量的关键调节因子。IP池的增加是由祖细胞细胞质室中Axin和GSK-3的相互作用介导的。重要的是，随着发育的进行，轴蛋白在细胞核中富集，通过β -连环蛋白激活触发神经元分化。Axin在Thr485位点的cdk5依赖性磷酸化严格控制着Axin的核定位和IPs从增殖状态到分化状态的转换。我们的研究结果证明了神经发生中重要的轴蛋白依赖调节机制，为大脑皮层的进化扩张提供了潜在的见解。
The expansion of the mammalian cerebral cortex is safeguarded by a concerted balance between amplification and neuronal differentiation of intermediate progenitors (IPs). Nonetheless, the molecular controls governing these processes remain unclear. We found that the scaffold protein Axin is a critical regulator that determines the IP population size and ultimately the number of neurons during neurogenesis in the developing cerebral cortex. The increase of the IP pool is mediated by the interaction between Axin and GSK-3 in the cytoplasmic compartments of the progenitors. Importantly, as development proceeds, Axin becomes enriched in the nucleus to trigger neuronal differentiation via beta-catenin activation. The nuclear localization of Axin and hence the switch of IPs from proliferative to differentiative status are strictly controlled by the Cdk5-dependent phosphorylation of Axin at Thr485. Our results demonstrate an important Axin-dependent regulatory mechanism in neurogenesis, providing potential insights into the evolutionary expansion of the cerebral cortex.