(E) Proposed model of sequentially acting SOX proteins in neuronal and glial lineage specification. Silent neuronal, astrocyte and oligodendrocyte genes are all prebound by SOX3 in NPCs. In GPCs transactivating astrocytic enhancers, enriched for NFI motifs, (CRM A) become additionally targeted by SOX9 whereas non-activating astrocytic enhancers (CRMB) or CRMs around oligodendrocyte genes become pre-bound by SOX9 only. While SOX3 represses the activation of prebound genes, neuronal and glial gene expression become activated when SOX3 is downregulated and a cellular context of activating transcription factors has developed, which according to the model can consist of SOX11 in neurons, SOX10 in oligodendrocytes and NFIA and SOX9 in astrocytes. It should be noted that we do not provide any evidence that SOX3/SOX9 or NFIA/SOX9 physically interact or co-bind DNA 