双皮质素样激酶与双皮质素共同作用，介导纤维束交叉和神经元迁移。

Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration.

作者信息

Koizumi Hiroyuki, Tanaka Teruyuki, Gleeson Joseph G

机构信息

Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, La Jolla, California 93093, USA.

出版信息

Neuron. 2006 Jan 5;49(1):55-66. doi: 10.1016/j.neuron.2005.10.040.

DOI:10.1016/j.neuron.2005.10.040

PMID:16387639

Abstract

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.

摘要

编码一种微管相关蛋白的双皮质素（Dcx）在大脑发育中的潜在作用一直存在争议。携带突变的人类表现出皮质分层的深刻改变，而在小鼠中，RNA干扰介导的敲低而非种系敲除显示皮质神经元定位异常。在此，我们报告双皮质素样激酶（Dclk）基因在轴突跨越中线投射形成和皮质神经元迁移过程中与Dcx在部分冗余途径中发挥作用。在半球间连接以及皮质和皮质下衍生神经元的迁移中均观察到剂量依赖性遗传效应。令人惊讶的是，RNA干扰介导的任一基因敲低都会导致相似的迁移缺陷。这些结果表明，Dcx微管相关蛋白家族对于神经元的正常迁移和轴突布线是必需的。