Fate determination and migration of progenitors in the postnatal mammalian CNS

Using replication-deficient retroviruses to transfer marker genes into immature cells, we have characterized spatial and temporal patterns of glial progenitor migration and differentiation in the early postnatal rat forebrain and cerebellum, and interneuron differentiation in the cerebellum. Progenitors do not migrate randomly, but follow discrete paths, largely confined to a coronal plane in forebrain and a sagittal plane in cerebellum. Radial glia provide one substrate for migration. In vitro studies suggest that radial glia contribute a permissive pathway along which migratory progenitors can travel and that contact with radial glia keeps progenitors in an immature, migratory state. Local environmental cues that progenitors encounter during migration may influence fate decisions substantially. Not all progenitors differentiate; some remain in an immature, proliferative state in which they do not complete differentiation, but can be induced to do so by pathological conditions.