Cajal-Retzius cells regulate the radial glia phenotype in the adult and developing cerebellum and alter granule cell migration.

Studies on the reeler mutation have shown that pioneer Cajal-Retzius (CR) cells are involved in neuronal migration in the developing cortex. Here, we use grafting and coculture experiments to investigate the mechanisms by which CR cells govern migration. We show that transplantation of embryonic CR cells, but not other cortical neurons, into adult cerebella induces a transient rejuvenation of host Bergmann glia into a radial glia phenotype. Similarly, CR cells sustain the phenotype of developing radial glia in postnatal cerebellar slices and induce the organization of a glial scaffold inside the CR cell explants. Studies with semipermeable inserts show that these effects are mediated by diffusible signals. We also show that CR cells adjacent to the surface of cerebellar slices reverse the direction of the migration of granule cells. Finally, CR cells from reeler mutant embryos elicited similar effects. These observations imply a role for CR cells in the regulation of the radial glia phenotype, a key step for neuronal migration, and suggest that these pioneer neurons may also exert a chemoattractive influence on migrating neurons.