Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex
Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex
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DOI：
10.1016/j.neuron.2013.12.015
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发表时间：
2014-02-19
期刊：
影响因子：
16.2
通讯作者：
Kaibuchi, Kozo
中科院分区：
文献类型：
--
作者：
Namba, Takashi;Kibe, Yuji;Kaibuchi, Kozo
神经元的极化主要包括轴突和树突的分化，受细胞自主和非细胞自主因素的调节。在发育中的中枢神经系统中，神经元的发育发生在一个不同的环境中，这个环境还包括细胞外基质、放射状胶质细胞和神经元。虽然已经确定了许多影响神经元极化的细胞自主因素，但参与神经元极化的微环境线索在很大程度上仍不清楚。在这里，我们发现神经元极化发生在下中间带的微环境中，在那里细胞黏附分子瞬时轴突糖蛋白-1(TAG-1)在皮质传出轴突中表达。多极细胞的未成熟轴突与Tag-1阳性轴突紧密接触并产生轴突。抑制Tag-1介导的细胞间相互作用或其下游的激酶Lyn会损害神经元的极化。这些结果表明，Tag-1介导的未极化多极细胞与先锋轴突之间的细胞间相互作用部分通过Lyn激酶和rac1调节多极细胞的极化。
The polarization of neurons, which mainly includes the differentiation of axons and dendrites, is regulated by cell-autonomous and non-cell-autonomous factors. In the developing central nervous system, neuronal development occurs in a heterogeneous environment that also comprises extracellular matrices, radial glial cells, and neurons. Although many cell-autonomous factors that affect neuronal polarization have been identified, the microenvironmental cues involved in neuronal polarization remain largely unknown. Here, we show that neuronal polarization occurs in a microenvironment in the lower intermediate zone, where the cell adhesion molecule transient axonal glycoprotein-1 (TAG-1) is expressed in cortical efferent axons. The immature neurites of multipolar cells closely contact TAG-1-positive axons and generate axons. Inhibition of TAG-1-mediated cell-to-cell interaction or its downstream kinase Lyn impairs neuronal polarization. These results show that the TAG-1-mediated cell-to-cell interaction between the unpolarized multipolar cells and the pioneering axons regulates the polarization of multipolar cells partly through Lyn kinase and Rac1.