RNAi reveals doublecortin is required for radial migration in rat neocortex
RNAi reveals doublecortin is required for radial migration in rat neocortex
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DOI：
10.1038/nn1153
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发表时间：
2003-12-01
影响因子：
25
通讯作者：
LoTurco, JJ
中科院分区：
文献类型：
--
作者：
Bai, JL;Ramos, RL;LoTurco, JJ
人类双皮质素基因（DCX）的突变会导致大脑新皮质畸形。矛盾的是，在小鼠中基因敲除Dcx并不会导致新皮质畸形。我们利用编码短发夹RNA的质粒进行电穿孔，在子宫内对DCX蛋白产生干扰（RNA干扰），并且我们发现DCX是发育中的大鼠新皮质中神经元放射状迁移所必需的。DCX的RNA干扰会导致放射状迁移中细胞自主性和非细胞自主性的破坏，并在新皮质发育中产生两种破坏。首先，许多神经元过早停止迁移，在中间带进而在白质内形成皮质下带状异位。其次，许多神经元迁移到正常位置皮质内不适当的新皮质层。因此，子宫内RNA干扰可有效地用于研究DCX在新皮质发育中的特定细胞作用，并可构建双皮质综合征的动物模型。
Mutations in the doublecortin gene (DCX) in humans cause malformation of the cerebral neocortex. Paradoxically, genetic deletion of Dcx in mice does not cause neocortical malformation. We used electroporation of plasmids encoding short hairpin RNA to create interference (RNAi) of DCX protein in utero, and we show that DCX is required for radial migration in developing rat neocortex. RNAi of DCX causes both cell-autonomous and non-cell autonomous disruptions in radial migration, and creates two disruptions in neocortical development. First, many neurons prematurely stop migrating to form subcortical band heterotopias within the intermediate zone and then white matter. Second, many neurons migrate into inappropriate neocortical lamina within normotopic cortex. In utero RNAi can therefore be effectively used to study the specific cellular roles of DCX in neocortical development and to produce an animal model of double cortex syndrome.