Bai Jilin, Ramos Raddy L, Ackman James B, Thomas Ankur M, Lee Richard V, LoTurco Joseph J
Department of Physiology and Neurobiology, University of Connecticut, 3107 Horsebarn Hill Road, U-4156, Storrs, Connecticut 06269, USA.
Nat Neurosci. 2003 Dec;6(12):1277-83. doi: 10.1038/nn1153. Epub 2003 Nov 16.
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.
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，小鼠中Dcx基因的缺失并不会导致新皮质畸形。我们通过电穿孔编码短发夹RNA的质粒，在子宫内对DCX蛋白进行干扰（RNA干扰），结果表明，DCX是发育中的大鼠新皮质中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和非细胞自主的破坏，并在新皮质发育中产生两种破坏。第一，许多神经元过早停止迁移，在中间带内形成皮质下带异位，然后出现在白质中。第二，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，并建立双皮质综合征的动物模型。
