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RNAi reveals doublecortin is required for radial migration in rat neocortex

Nature Neuroscience volume 6, pages 1277–1283 (2003)Cite this article

Abstract

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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Figure 1: In vivo RNAi of DCX protein expression by in utero electroporation of plasmids encoding short hairpin RNA.
Figure 2: Disrupted radial migration by RNAi of DCX.
Figure 3: Morphology of neurons in hemispheres targeted with RNAi of DCX.
Figure 4: Non-cell-autonomous component of migration disruption by RNAi of DCX.
Figure 5: Creation of double cortex syndrome by RNAi of DCX.
Figure 6: RNAi of DCX in mice disrupts radial migration in neocortex.

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Acknowledgements

R.L.R. and J.B.A. contributed equally to this work. We thank S. Korn, A. Moiseff and M. Paramasivam for helpful discussions and comments on drafts of the manuscript. We also thank D. Turner for the mU6pro vector. This work was supported by the National Institute of Mental Health (MH056524 to J.J.L.) and the National Institute of Child Health and Human Development (HD20806).

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  1. Department of Physiology and Neurobiology, University of Connecticut, 3107 Horsebarn Hill Road, U-4156, Storrs, Connecticut, 06269, USA

    Jilin Bai, Raddy L Ramos, James B Ackman, Ankur M Thomas, Richard V Lee & Joseph J LoTurco

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  1. Jilin Bai
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Correspondence to Joseph J LoTurco.

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Bai, J., Ramos, R., Ackman, J. et al. RNAi reveals doublecortin is required for radial migration in rat neocortex. Nat Neurosci 6, 1277–1283 (2003). https://doi.org/10.1038/nn1153

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