doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration
doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration
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DOI：
10.1016/j.neuron.2005.10.040
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发表时间：
2006-01-05
期刊：
影响因子：
16.2
通讯作者：
Gleeson, JG
中科院分区：
文献类型：
--
作者：
Koizumi, H;Tanaka, T;Gleeson, JG
双皮质素（Dcx），编码微管相关蛋白，在大脑发育中的潜在作用仍然存在争议。具有突变的人类显示皮质层压的深刻改变，而在小鼠中，RNAi介导的敲除而不是种系敲除显示皮质神经元的异常定位。在这里，我们报告，doublecortin样激酶（Dcx）基因的功能在一个部分冗余的途径与Dcx在形成轴突投射的中线和迁移的皮层神经元。剂量依赖性的遗传效应中观察到大脑半球间的连接和迁移的皮质和皮质下衍生的神经元。令人惊讶的是，RNAi介导的基因敲低导致类似的迁移缺陷。这些结果表明，Dcx微管相关蛋白家族是必要的适当的神经元迁移和轴突布线。
The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.