Multipotent stem cells from the mouse basal forebrain contribute GABAergicneurons and oligodendrocytes to the cerebral cortex during embryogenesis

During CNS development, cell migrations play an important role, adding to t he cellular complexity of different regions. Earlier studies have shown a r obust migration of cells from basal forebrain into the overlying dorsal for ebrain during the embryonic period. These immigrant cells include GABAergic neurons that populate the cerebral cortex and hippocampus. In this study w e have examined the fate of other basal forebrain cells that migrate into t he dorsal forebrain, identifying basal cells using an antibody that recogni zes both early (dlx1/2) and late (dlx 5/6) members of the dlx homeobox gene family. We found that a subpopulation of cortical and hippocampal oligoden drocytes are also ventral-derived. We traced the origin of these cells to b asal multipotent stem cells capable of generating both GABAergic neurons an d oligodendrocytes. A clonal analysis showed that basal forebrain stem cell s produce significantly more GABAergic neurons than dorsal forebrain stem c ells from the same embryonic age. Moreover, stem cell clones from basal for ebrain are significantly more likely to contain both GABAergic neurons and oligodendrocytes than those from dorsal. This indicates that forebrain stem cells are regionally specified. Whereas dlx expression was not detected wi thin basal stem cells growing in culture, these cells produced dlx-positive products that are capable of migration. These data indicate that the devel oping cerebral cortex incorporates both neuronal and glial products of basa l forebrain and suggest that these immigrant cells arise from a common prog enitor, a dlx-negative basal forebrain stem cell.