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Developmental dyslexia is a language learning disorder that affects approximately 4–10% of the population. A number of candidate dyslexia susceptibility genes have been identified, including  DCDC2  and  KIAA0319  on Chromosome (Chr) 6p22.2 and  DYX1C1  on Chr 15q21. Embryonic knockdown of the function of homologs of these genes in rat neocortical projection cell progenitors by  in utero  electroporation of plasmids encoding small hairpin RNA (shRNA) revealed that all three genes disrupted neuronal migration to the neocortex. Specifically, this disruption would result in heterotopia formation ( Dyx1c1  and  Kiaa0319 ) and/or overmigration past their expected laminar location ( Dyx1c1  and  Dcdc2 ). In these experiments, neurons normally destined for the upper neocortical laminæ were transfected on embryonic day (E) 15.5, and we designed experiments to test whether these migration phenotypes were the result of targeting a specific type of projection neuron. We transfected litters with  Dcdc2  shRNA,  Dyx1c1  shRNA,  Kiaa0319  shRNA, or fluorescent protein (as a control) at each of three gestational ages (E14.5, E15.5, or E16.5). Pups were allowed to come to term, and their brains were examined at 3 weeks of age for the position of transfected cells. We found that age of transfection did not affect the percentage of unmigrated neurons—transfection with  Kiaa0319  shRNA resulted in heterotopia formation at all three ages. Overmigration of neurons transfected with  Dcdc2  shRNA, while present following transfections at the later ages, did not occur following E14.5 transfections. These results are considered in light of the known functions of each of these candidate dyslexia susceptibility genes.

Position of Neocortical Neurons Transfected at Different Gestational Ages with shRNA Targeted against Candidate Dyslexia Susceptibility Genes