EXPRESSION AND FUNCTION OF THE X-LINKED SUBCORTICAL LAMINAR HETEROTOPIA GENE (DOUBLECORTIN) IN IMMORTALIZED NEURONS

Doublecortin (dcx) is the gene responsible of the main forms of X-linked subcortical laminar heterotopia ('double cortex'), a genetic disease affecting brain cortex development due to a defect of neuronal migration. The gene encodes for microtubule-associated proteins (DCX) whose precise mechanism of action is still unknown. In premiminar experiments, we found that mouse immortalized immature neurons (GN11 cells), that show migratory activity "in vitro", do not express dcx, providing a useful tool to investigate DCX functions. Transfection of a GFP-dcx expression vector in GN11 cells shows that the protein colocalizes with tubulin and increases the organization of microtubular structures. Time-lapse recording analysis shows that DCX-labelled microtubules undergo an intense rearrangement during random movement of the cells. However, DCX overexpression increases the directional migration (chemotaxis) of GN11 cells toward a gradient of FBS, and under these conditions DCX appears dispersed in the cytoplasm of lamellipodia-rich cells. In conclusion, these results indicate that DCX plays a pleiotropic and dynamic function in the control of the movement and migration of GN11 neurons. (Grants: Telethon E523, MIUR-COFIN, FIRB).