Role of EFHC1 in the control of tangential migration in the developing rat brain

Abstract

EFHC1 has been linked to juvenile myoclonic epilepsy, but the physiological function of the protein is still unknown. So, the role of EFHC1 in the tangential migration of inhibitory interneurons in the developing rat brain was examined by modulating its expression in the basal telencephalon (BT) using ex vivo and focal electroporation. Both loss of function experiments using shRNA and gain of function experiments overexpressing EFHC1 were performed. EFHC1 knockdown in the BT caused a disruption of tangentially migrating neurons compared with the control condition. A rescue experiment demonstrated that this effect was due to EFHC1 loss of function. Overexpression of EFHC1 had no effect on the migratory process of these neurons. A TUNEL assay revealed that EFHC1 knockdown does not induce apoptosis in the BT. These results indicate that EFHC1 is involved in the nucleokinesis of tangentially migrating interneurons and strengthen the hypothesis that JME is a developmental disorder.