DYX1C1 functions in neuronal migration in developing neocortex.
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.
Wang
Y
Y
Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06268, USA.
Paramasivam
M
M
Thomas
A
A
Bai
J
J
Kaminen-Ahola
N
N
Kere
J
J
Voskuil
J
J
Rosen
G D
GD
Galaburda
A M
AM
Loturco
J J
JJ
D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D001973:Bromodeoxyuridine / Q000378:metabolism; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002522:Chlorocebus aethiops; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental; D016296:Mutagenesis; D019579:Neocortex / Q000166:cytology / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D038081:Organogenesis; D017434:Protein Structure, Tertiary / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D014162:Transfection / Q000379:methods
D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D001973:Bromodeoxyuridine