平衡Akt:如何微调神经元迁移速度。

Neurogenesis (Austin, Tex.) Pub Date : 2016-11-22 eCollection Date: 2016-01-01 DOI:10.1080/23262133.2016.1256854
Yasuhiro Itoh
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引用次数: 7

摘要

在发育中的哺乳动物新皮层中,大脑深处由神经干/祖细胞产生的新生神经元开始了一段漫长的旅程,到达它们在大脑表面的最终目的地。这一被称为径向神经元迁移的过程是皮层中适当层和网络形成的先决条件,其失调与皮质畸形和神经系统疾病有关。考虑到皮层神经元细胞类型的时间顺序与其空间分布之间的良好相关性,尽管潜在的分子机制尚未完全了解,但需要严格控制迁移速度以实现正确的新皮层分层。最近,我们发现Akt激酶及其激活剂PDK1调节小鼠新皮质神经元通过皮质板的迁移速度。我们进一步发现PDK1-Akt通路控制迁移过程中细胞核和中心体的协调运动。我们的数据还表明,PDK1-Akt通路对神经元迁移的控制是在微管水平上介导的,可能是通过调节细胞质动力蛋白/动力蛋白复合物来实现的。因此,我们的研究结果确定了控制神经元迁移速度的信号通路,以及Akt信号传导与细胞质动力蛋白/动力蛋白复合物之间的新联系。
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A balancing Akt: How to fine-tune neuronal migration speed.

In the developing mammalian neocortex, newborn neurons produced deep in the brain from neural stem/progenitor cells set out for a long journey to reach their final destination at the brain surface. This process called radial neuronal migration is prerequisite for the formation of appropriate layers and networks in the cortex, and its dysregulation has been implicated in cortical malformation and neurological diseases. Considering a fine correlation between temporal order of cortical neuronal cell types and their spatial distribution, migration speed needs to be tightly controlled to achieve correct neocortical layering, although the underlying molecular mechanisms remain not fully understood. Recently, we discovered that the kinase Akt and its activator PDK1 regulate the migration speed of mouse neocortical neurons through the cortical plate. We further found that the PDK1-Akt pathway controls coordinated movement of the nucleus and the centrosome during migration. Our data also suggested that control of neuronal migration by the PDK1-Akt pathway is mediated at the level of microtubules, possibly through regulation of the cytoplasmic dynein/dynactin complex. Our findings thus identified a signaling pathway controlling neuronal migration speed as well as a novel link between Akt signaling and cytoplasmic dynein/dynactin complex.

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