Factors affecting the morphology of radial glia

A model of cortical dysplasia results from disruption of the earliest generated neocortical cells. Injections of an antimitotic (methylazoxy methanol - MAM) into pregnant ferrets result in a constellation of effects, which include disruption of radial glia, with early differentiation in astrocytes, and impaired migration of neurons into the cortical plate. We found previously that culture of PO MAM-treated slices with explants of normal cortical plate reorganizes the radial glia toward their normal morphology and improves migration of neurons into the cortical plate. This suggested that PO normal cortical plate contains a 'factor' capable of providing reorganizing cues to disorganized developing cortex. The current study characterizes the biological activity in normal cortical plate by isolating fractions of different molecular weight obtained from conditioned media of organotypic cultures. The only media fraction capable of providing reorganizing activity to MAM-treated cortex was the molecular weight fraction between 30 and 50 kDa. Treatment designed to denature proteins demonstrated that the active molecular weight fraction (30-50 kDa) was not able to provide reorganizing cues when either heated or treated with Proteinase K. These data provide support for the idea that normal cortical plate of neonatal ferret contains a radialization factor that is a protein of 30-50 kDa.