POSTNATAL ANALYSIS OF THE EFFECT OF EMBRYONIC KNOCKDOWN AND OVEREXPRESSION OF CANDIDATE DYSLEXIA SUSCEPTIBILITY GENE DCDC2
Embryonic knockdown of candidate dyslexia susceptibility gene (CDSG) homologs in cerebral cortical progenitor cells in the rat results in acute disturbances of neocortical migration. In the current report we investigated the effects of embryonic knockdown and overexpression of the homolog of DCDC2 ,...
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Published in | Neuroscience Vol. 152; no. 3; pp. 723 - 733 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
19.01.2008
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Online Access | Get full text |
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Summary: | Embryonic knockdown of candidate dyslexia susceptibility gene (CDSG) homologs in cerebral cortical progenitor cells in the rat results in acute disturbances of neocortical migration. In the current report we investigated the effects of embryonic knockdown and overexpression of the homolog of
DCDC2
, one of the CDSGs, on the postnatal organization of the cerebral cortex. Using a within-litter design, we transfected cells in rat embryo neocortical ventricular zone around E15 with either 1) small hairpin RNA (shRNA) vectors targeting
Dcdc2
, 2) a DCDC2 overexpression construct, 3)
Dcdc2
shRNA along with DCDC2 overexpression construct, 4) an overexpression construct comprised of the C Terminal domain of DCDC2, or 5) an overexpression construct comprised of the DCX Terminal domain of DCDC2. RNAi of
Dcdc2
resulted in pockets of heterotopic neurons in the periventricular region. Approximately 25% of the transfected brains had hippocampal pyramidal cell migration anomalies.
Dcdc2
shRNA-transfected neurons migrated in a bimodal pattern, with approximately 7% of the neurons migrating a short distance from the ventricular zone, and another 30% migrating past their expected lamina. Rats transfected with
Dcdc2
shRNA along with the DCDC2 overexpression construct rescued the periventricular heterotopia phenotype, but did not affect the percentage of transfected neurons that migrate past their expected laminar location. There were no malformations associated with any of the overexpression constructs, nor was there a significant laminar disruption of migration. These results support the claim that knockdown of
Dcdc2
expression results in neuronal migration disorders similar to those seen in the brains of dyslexics. |
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Bibliography: | Section Editor: John L.R. Rubenstein |
ISSN: | 0306-4522 |
DOI: | 10.1016/j.neuroscience.2008.01.020 |