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 me chanisms by which CR cells govern migration. We show that transplantat ion 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 o rganization of a glial scaffold inside the CR cell explants. Studies w ith semipermeable inserts show that these effects are mediated by diff usible signals. We also show that CR cells adjacent to the surface of cerebellar slices reverse the direction of the migration of granule ce lls. Finally, CR cells from reeler mutant embryos elicited similar eff ects. These observations imply a role for CR cells in the regulation o f the radial glia phenotype, a key step for neuronal migration, and su ggest that these pioneer neurons may also exert a chemoattractive infl uence on migrating neurons.