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Figure 4


Fig. 3. Proneural proteins control multiple cellular processes and activate multiple target genes during neurogenesis. Proneural proteins control many aspects of neurogenesis and some of their targets have been identified. (A) Proneural proteins suppress the neural stem cell programme by interfering with the activity of SoxB1 genes (see text); they select neuronal progenitors by directly activating Notch ligands and suppress astrogenesis by interfering with SMAD and STAT signalling (see text). (B) Different proneural proteins specify different neuronal subtype identities by directly activating HD protein-encoding genes, such as Hb9 (Lee and Pfaff, 2003), Dlx1/2 (Poitras et al., 2007) and Mbh1 (also known as Barhl2) (Saba et al., 2005). (C) Proneural proteins also induce the expression of transcription factors that promote neuronal differentiation, including bHLH proteins, T-box proteins and Sox proteins (see text). In addition to regulating transcription factors involved in cell fate specification, proneural proteins also regulate genes that control later steps in the neurogenic programme, such as cell cycle arrest, neuronal differentiation and migration (Farah et al., 2000; Castro et al., 2006; Ge et al., 2006). Some of these genes (e.g. Fbxw7 and doublecortin-like kinase) are regulated cooperatively by the proneural protein Mash1 and the POU HD proteins Brn1 (also known as Pou3f3) and Brn2 (Castro et al., 2006). Tbr2 (Eomes); Dcamkl1 (Dclk1).