Tbr2-positive intermediate (basal) neuronal progenitors safeguard cerebral cortex expansion by controlling amplification of pallial glutamatergic neurons and attraction of subpallial GABAergic interneurons
Tbr2-positive intermediate (basal) neuronal progenitors safeguard cerebral cortex expansion by controlling amplification of pallial glutamatergic neurons and attraction of subpallial GABAergic interneurons
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DOI：
10.1101/gad.575410
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发表时间：
2010-08-15
影响因子：
10.5
通讯作者：
Broccoli, Vania
中科院分区：
文献类型：
--
作者：
Sessa, Alessandro;Mao, Chai-An;Broccoli, Vania
在发育和进化过程中大脑皮层进行惊人的扩张时，它如何能够在兴奋性神经元和抑制性神经元之间维持正确的平衡，人们对此知之甚少。事实上，前者在皮质原基内产生，而后者在腹侧苍白球外侧产生。因此，这两种神经元群体如何协调它们的相对数量以构建一个功能性的皮质网络，仍有待解决。在此，我们表明，Tbr2阳性的皮质中间（基底）神经元祖细胞（INP）决定迁移路径，并通过一种非细胞自主机制控制室下区（SVZ）内苍白球下区γ - 氨基丁酸（GABA）能中间神经元的数量。事实上，Tbr2中间神经元的吸引活性受Cxcl12趋化因子信号的调节，在Tbr2突变体中强制表达Cxcl12在一定程度上可以挽救SVZ细胞的迁移。因此我们提出，INP能够同时控制谷氨酸能和GABA能神经元库的增加，从而创造一种内在平衡它们相对积累的简单方法。
Little is known about how, during its formidable expansion in development and evolution, the cerebral cortex is able to maintain the correct balance between excitatory and inhibitory neurons. In fact, while the former are born within the cortical primordium, the latter originate outward in the ventral pallium. Therefore, it remains to be addressed how these two neuronal populations might coordinate their relative amounts in order to build a functional cortical network. Here, we show that Tbr2-positive cortical intermediate (basal) neuronal progenitors (INPs) dictate the migratory route and control the amount of subpallial GABAergic interneurons in the subventricular zone (SVZ) through a non-cell-autonomous mechanism. In fact, Tbr2 interneuron attractive activity is moderated by Cxcl12 chemokine signaling, whose forced expression in the Tbr2 mutants can rescue, to some extent, SVZ cell migration. We thus propose that INPs are able to control simultaneously the increase of glutamatergic and GABAergic neuronal pools, thereby creating a simple way to intrinsically balance their relative accumulation.