The subventricular zone (SVZ) in the neonatal mammalian forebrain simultaneously generates olfactory interneurons, astrocytes, and oligodendrocytes. The molecular cues that enable SVZ progenitors to generate three distinct cell lineages without a temporal switching mechanism are not known. Here, we demonstrate that the basic helix-loop-helix transcription factor Olig2 plays a central role in this process. Olig2 is specifically expressed in gliogenic progenitors in the postnatal SVZ and by all glial lineages derived from this structure. By expressing normal and dominant-interfering forms of Olig2 in vivo, we show that Olig2 repressor function is both sufficient and necessary to prevent neuronal differentiation and to direct SVZ progenitors toward astrocytic and oligodendrocytic fates. Although Olig2 activity has been associated previously with motor neuron and oligodendrocyte development, our findings establish a previously unappreciated role for Olig2 in the development of astrocytes. Furthermore, these results indicate that Olig2 serves a critical role in pan-glial versus neuronal fate decisions in SVZ progenitors, making it the first intrinsic fate determinant shown to operate in the early postnatal SVZ.

The precise origins of postnatal subventricular zone (SVZ) cells are not known. Furthermore, the gliogenic potential of progenitors expressing Dlx genes that migrate ventrodorsally from the ganglionic eminences has not been explored in vivo. Here, we identify the embryonic origins of two distinct populations of postnatal SVZ cells: SVZ border cells, which express Zebrin II, and migratory cells in the central SVZ, which are generally devoid of Zebrin II expression (Staugaitis et al., 2001). Zebrin II is expressed by all cells of the telencephalic primordium, with its expression becoming restricted to astrocytes in the mature telencephalon. As the neuroepithelium folds during corticostriatal sulcus formation (embryonic day 13-15), a wedge of Zebrin II+ cells is created at the presumptive site of the dorsolateral SVZ. At this time, Dlx2-expressing cells and their progeny begin to migrate ventrodorsally along a medial path from the ganglionic eminences. These migratory subpallial cells invade the wedge of Zebrin II+ cells to form the central region of the SVZ. We used a Dlx2/tauLacZ knock-in to perform a short-term lineage analysis of Dlx2-expressing cells throughout SVZ formation and the postnatal peak of gliogenesis. Dlx2/tauLacZ [beta-galactosidase (beta-gal)]-expressing cells populate the central SVZ, whereas Zebrin II-expressing cells form its borders. Furthermore, beta-gal expression demonstrates a lineage relationship between Dlx2-expressing cells and glia residing in the dorsal telencephalon. We propose a model for the formation of the postnatal SVZ and demonstrate that subpallium-derived Dlx2-expressing cells give rise to astrocytes and oligodendrocytes in the white matter and cerebral cortex.

The subventricular zone (SVZ) of the perinatal forebrain gives rise to both neurons and glia. The mechanisms governing the phenotypic specification of progenitors within this heterogeneous germinal zone are unclear. However, the characterization of subpopulations of SVZ cells has given us a better understanding of the basic architecture of the SVZ and presents us with the opportunity to ask more detailed questions regarding phenotype specification and cell fate. Recent work demonstrating the embryonic origins of SVZ cells is summarized, and a model describing the formation of the perinatal SVZ, noting contributions of cells from pallial as well as subpallial germinal zones, is presented. We further address differences among classes of SVZ cells based on molecular profile, phenotype, and migration behavior and present a model summarizing the organization of perinatal SVZ cells along coronal, sagittal, and horizontal axes. A detailed description of the SVZ in the adult, outlining classes of cells based on morphology, molecular profile, and proliferative behavior, was recently reported by Doetsch et al. (Proc Natl Acad Sci USA 93:14895-14900, 1997). Potential relationships among cells within the perinatal and adult SVZ will be discussed. GLIA 43:52-61, 2003.