Article

DYX1C1 functions in neuronal migration in developing neocortex

Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06268, USA; Department of Medical Genetics, Biomedicum, University of Helsinki, Helsinki, Finland; Department of Biosciences and Nutrition, and Clinical Research Centre, Karolinska Institutet; Everest Biotech Ltd., Cherwell Innovation Centre, 77 Heyford Park, Upper Heyford, Oxfordshire, OX25 5HD, UK; The Division of Behavioral Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
Neuroscience DOI:10.1016/j.neuroscience.2006.08.022 pp.515-522

ABSTRACT Rodent homologues of two candidate dyslexia susceptibility genes, Kiaa0319 and Dcdc2, have been shown to play roles in neuronal migration in developing cerebral neocortex. This functional role is consistent with the hypothesis that dyslexia susceptibility is increased by interference with normal neural development. In this study we report that in utero RNA interference against the rat homolog of another candidate dyslexia susceptibility gene, DYX1C1, disrupts neuronal migration in developing neocortex. The disruption of migration can be rescued by concurrent overexpression of DYX1C1, indicating that the impairment is not due to off-target effects. Transfection of C- and N-terminal truncations of DYX1C1 shows that the C-terminal TPR domains determine DYX1C1 intracellular localization to cytoplasm and nucleus. RNAi rescue experiments using truncated versions of DYX1C1 further indicate that the C-terminus of DYX1C1 is necessary and sufficient to DYX1C1’s function in migration. In conclusion, DYX1C1, similar to two other candidate dyslexia susceptibility genes, functions in neuronal migration in rat neocortex.

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Keywords

C-terminal TPR domains
 
C-terminus
 
candidate dyslexia susceptibility gene
 
candidate dyslexia susceptibility genes
 
disruption
 
disrupts neuronal migration
 
dyslexia susceptibility
 
DYX1C1 intracellular localization
 
DYX1C1’s function
 
functional role
 
N-terminal truncations
 
neuronal migration
 
normal neural development
 
rat homolog
 
rat neocortex
 
RNAi rescue experiments
 
Rodent homologues
 
roles
 
sufficient
 
utero RNA interference