RNAi reveals doublecortin is required for radial migration in rat neocortex.
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.
Bai
Jilin
J
Department of Physiology and Neurobiology, University of Connecticut, 3107 Horsebarn Hill Road, U-4156, Storrs, Connecticut 06269, USA.
Ramos
Raddy L
RL
Ackman
James B
JB
Thomas
Ankur M
AM
Lee
Richard V
RV
LoTurco
Joseph J
JJ
D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000502:physiology*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005260:Female; D017353:Gene Deletion; D008869:Microtubule-Associated Proteins; D019579:Neocortex / Q000166:cytology* / Q000196:embryology / Q000254:growth & development / Q000502:physiology*; D009479:Neuropeptides / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D011247:Pregnancy; D034622:RNA Interference; D051381:Rats; D017208:Rats, Wistar
C000714328:DCX protein, human; C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides