The role of radial glial cells as guides for migrating neurons is well established, whereas their role as precursor cells is less understood. Here we examined the composition of radial glial cells and their proliferation in the mouse telencephalon during development. We found that almost all radial glial cells proliferate throughout neurogenesis. They consist of three distinct subsets identified by immunostaining for the antigens RC2, the astrocyte-specific glutamate transporter (GLAST), and the brain-lipid-binding protein (BLBP). In addition, RC2, GLAST, and BLBP antisera label precursor cells with different morphologies and thereby cover almost the entire progenitor pool in the developing cerebral cortex. The subsets identified by differential expression of these antigens differ also in their transcription factor expression and cell cycle characteristics. Moreover, the content of BLBP seems correlated to the fate of the progeny. BLBP-negative precursors are detected only during neurogenesis and persist into postnatal stages solely in the rostral migratory stream, a region of ongoing neurogenesis. In contrast, an enriched population of multipotential cells, neurosphere cultures derived from the adult or embryonic telencephalon, is immunoreactive for RC2, GLAST, and BLBP. Taken together, we have identified novel, functionally distinct subsets of CNS precursor cells.

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.

The precursor function of the ubiquitous glial cell type in the developing central nervous system (CNS), the radial glia, is largely unknown. Using Cre/loxP in vivo fate mapping studies, we found that radial glia generate virtually all cortical projection neurons but not the interneurons originating in the ventral telencephalon. In contrast to the cerebral cortex, few neurons in the basal ganglia originate from radial glia, and in vitro lineage analysis revealed intrinsic differences in the potential of radial glia from the dorsal and ventral telencephalon. This shows that the progeny of radial glia not only differs profoundly between brain regions but also includes the majority of neurons in some parts of the CNS.

No abstract

The developing central nervous system of vertebrates contains an abundant cell type designated radial glial cells. These cells are known as guiding cables for migrating neurons, while their role as precursor cells is less clear. Since radial glial cells express a variety of astroglial characteristics and differentiate as astrocytes after completing their guidance function, they have been considered as part of the glial lineage. Using fluorescence-activated cell sorting, we show here that radial glial cells also are neuronal precursors and only later, after neurogenesis, do they shift towards an exclusive generation of astrocytes. These results thus demonstrate a novel function for radial glial cells, namely their ability to generate two major cell types found in the nervous system, neurons and astrocytes.