Fig. 9. A population of cortical astrocytes with GFAP upregulation is derived from Olig2-ablated cells. (A-D) Expression of Olig1 was examined by in situ hybridization in the coronal section of control and Olig2-ablated Cko^G cortices at P8 (A,B) and P14 (C,D). Arrowheads above and below the dashed line in indicate the superficial layers and the white matter in the cortex, respectively. (E,F) In situ hybridization for Olig1 and Gfap in the gray matter. Arrows above and below the longer dashed line indicate the superficial and deep cortical layers, respectively. (G) Schematic showing fate-mapping of Olig2-ablated cells after hGFAPCre-mediated recombination. Breeding of hGFAP-Cre mice with Olig2-floxed mice carrying the RosaYFP reporter gene (Srinivas et al., 2001) generated offspring with Olig2 ablation and activation of YFP expression in the same cells after Cre-mediated excision of loxP sites (black triangles). Red line indicates Olig2-3' UTR. (H) Immunostaining with antibodies to YFP and GFAP in the superficial cortical layers of Olig2-ablated triple-transgenic mice at P14. Arrowheads indicate cells co-labeled with YFP and GFAP. (I,J) Expression of Olig2-3' UTR and Gfap was examined by double in situ hybridization on sections of the Olig2-ablated cortex at P14. Arrows in I indicate Olig2-expressing cells in the deep cortical layers. Boxed area in I is shown at high magnification in J. Arrowheads in J indicate cells co-expressing Olig2-3' UTR and Gfap. (K) Schematic depicting cortical astrocyte development in relation to Olig2 expression. In the normal developing brain, Olig2 is expressed in cortical neural progenitor cells (NP). At early postnatal stages, Olig2 is expressed in immature developing astrocytes (A) at a high level. Beginning at postnatal week 2, the Olig2 expression level is reduced in astrocytes and GFAP expression becomes undetectable. In adulthood, Olig2 expression is absent in mature astrocytes, suggesting that the Olig2 expression level is downregulated in cortical astrocytes during the process of astrocyte maturation in brain development. GFAP downregulation in mature astrocytes suggests that other factors also negatively regulate GFAP expression in adulthood. In the absence of Olig2, GFAP expression is sustained or upregulated in a population of cortical astrocytes throughout adulthood. By contrast, Olig2 ablation results in a defect in the formation of white matter astrocyte subpopulations (lower panel).