No abstract

Precisely regulated radial migration out of the ventricular zone is essential for corticogenesis. Here, we identify a mechanism that can tether ventricular zone cells in situ. FILIP interacts with Filamin A, an indispensable actin-binding protein that is required for cell motility, and induces its degradation in COS-7 cells. Degradation of Filamin A is identified in the cortical ventricular zone, where filip mRNA is localized. Furthermore, most ventricular zone cells that overexpress FILIP fail to migrate in explants. These results demonstrate that FILIP functions through a Filamin A F-actin axis to control the start of neocortical cell migration from the ventricular zone.

During development neurons migrate from their site of origin to their final destinations under a variety of mechanisms. Although evidence has been accumulating that the cells from cortical ventricular zone (VZ) migrate radially and produce pyramidal cells, evidence that directly links the origin and the terminal phenotype of radially migrating cells has been limited. Further, the relation between the migratory behavior of these cells and their mature morphology remains obscure. To address these issues, we developed an in vitro preparation that enables visualization of cells derived from the cortical VZ. VZ cells of a rat cortex at embryonic days 18 to 19 were labeled by injecting green fluorescent protein (GFP)-encoding plasmid into the lateral ventricle, followed by electroporation. The cortex was then sliced and cultured organotypically. After 1 day, GFP(+) cells exhibited neural progenitor and radial glial cell natures. Over the next few days, many GFP(+) cells migrated toward the pial surface, extending leading processes toward the pial surface and leaving a thin trailing process that almost reached the VZ. The leading processes of these neurons were positive for microtubule-associated protein 2, and some transformed into dendritic arbor-like structures by day 5 or 6, and their trailing processes exhibited morphologic features indicative of prospective axons. Time-lapse analysis confirmed extension of the trailing processes. Expression of molecular markers and morphologic analysis demonstrated that the vast majority of the migrated GFP(+) cells differentiated into excitatory neurons with pyramidal cell-like morphology. These results strongly suggested that cells derived from the cortical VZ generate neurons that migrate radially. These neurons appeared to extend prospective dendrites in front and leave prospective axons behind, subsequently differentiating into pyramidal cells.