Influence of radial glia and Cajal-Retzius cells in neuronal migration

Normal development of cerebral cortex depends on proper sequential genesis of cortical neurons and glia. Disruption of corticogenesis in ferret by short-term arresting of cell division using injections of methylazoxy methanol (MAM) leads to a specific constellation of effects, including disruption and early differentiation of radial glia into astrocytes and disorganization of reelin-containing Cajal-Retzius cells. We hypothesize that early interference of normal cortical development removes a factor instrumental in maintaining radial glia in their normal elongated shape. In support of this idea, coculture of MAM-treated slices with normal cortical plate restores radial glia and Cajal-Retzius cells to their normal positions. Recently, we found that conditioned medium obtained from normal organotypic cultures returned radial glia toward their normal morphology only in a fraction of 30-50 kDa molecular weight (MW). To assess whether restoring this factor would also improve effective migration into the cortical plate of E24 MAM-treated animals, we conducted experiments using cocultures of normal cortical plate with organotypic cultures of MAM-treated cortex, which received prior BrdU injections. In both the normal and E24 MAM-treated/normal cortical plate coculture, a greater percentage of BrdU positive cells migrated effectively into the cortical plate. We suggest that early interruption of cell division eliminates a population of cells and a factor important for maintaining proper cortical development, specifically providing cues maintaining elongation of radial glia.