Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice
Branching and nucleokinesis defects in migrating interneurons derived from doublecortin knockout mice
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DOI：
10.1093/hmg/ddl062
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发表时间：
2006-05-01
影响因子：
3.5
通讯作者：
Francis, F
中科院分区：
文献类型：
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作者：
Kappeler, C;Saillour, Y;Francis, F
I 型无脑畸形是由双皮质素 (DCX) 和 LIS1 基因突变引起的。我们生成了 Dcx 基因敲除小鼠，以进一步了解与这种皮质畸形相关的病理生理机制。 DCx 在人类和小鼠大脑发育过程中的迁移中间神经元中表达。对这种源自内侧神经节隆起的切向迁移神经元群的视频显微镜分析显示出迁移动力学的缺陷。具体而言，在敲除细胞中，生长锥的形成和分裂导致新分支的产生更频繁，尽管分支不太稳定。因此，Dcx 缺陷的细胞以无序的方式迁移，延伸和缩回短分支，并使细胞核的长距离运动减少。尽管存在这些差异，迁移速度和距离仍然与野生型细胞相似。因此，这些新数据强调了 Dcx 的作用，Dcx 是一种微管相关蛋白，在迁移中间神经元的分支和核运动的前沿富集。
Type I lissencephaly results from mutations in the doublecortin (DCX) and LIS1 genes. We generated Dcx knockout mice to further understand the pathophysiological mechanisms associated with this cortical malformation. Dcx is expressed in migrating interneurons in developing human and mouse brains. Video microscopy analyses of such tangentially migrating neuron populations derived from the medial ganglionic eminence show defects in migratory dynamics. Specifically, the formation and division of growth cones, leading to the production of new branches, are more frequent in knockout cells, although branches are less stable. Dcx-deficient cells thus migrate in a disorganized manner, extending and retracting short branches and making less long-distant movements of the nucleus. Despite these differences, migratory speeds and distances remain similar to wild-type cells. These novel data thus highlight a role for Dcx, a microtubule-associated protein enriched at the leading edge in the branching and nucleokinesis of migrating interneurons.