Nature Neuroscience6, 1277 - 1283 (2003)
Published online: 16 November 2003; | doi:10.1038/nn1153
RNAi reveals doublecortin is required for radial migration in rat neocortex
Jilin Bai, Raddy L Ramos, James B Ackman, Ankur M Thomas, Richard V Lee
& Joseph J LoTurco
Department of Physiology and Neurobiology, University of Connecticut, 3107 Horsebarn Hill Road, U-4156, Storrs, Connecticut 06269, USA.
Correspondence should be addressed to Joseph J LoTurco loturco@uconn.edu
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.
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