Radial glial cells are characterized, besides their astroglial properties, by long radial processes extending from the ventricular zone to the pial surface, a crucial feature for the radial migration of neurons. The molecular signals that regulate this characteristic morphology, however, are largely unknown. We show an important role of the secreted molecule reelin for the establishment of radial glia processes. We describe a significant reduction in ventricular zone cells with long radial processes in the absence of reelin in the cortex of reeler mutant mice. These defects were correlated to a decrease in the content of brain lipid-binding protein (Blbp) and were detected exclusively in the cerebral cortex, but not in the basal ganglia of reeler mice. Conversely, reelin addition in vitro increased the Blbp content and process extension of radial glia from the cortex, but not the basal ganglia. Isolation of radial glia by fluorescent-activated cell sorting showed that these effects are due to direct signaling of reelin to radial glial cells. We could further demonstrate that this signaling requires Dab1, as the increase in Blbp upon reelin addition failed to occur in Dab1-/- mice. Taken together, these results unravel a novel role of reelin signaling to radial glial cells that is crucial for the regulation of their Blbp content and characteristic morphology in a region-specific manner.