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Bylund, M, Andersson, E, Novitch, BG and Muhr, J (2003) Vertebrate neurogenesis is counteracted by Sox1-3 activity. Nat. Neurosci. 6:1162-8
The generation of neurons from stem cells involves the activity of proneural basic helix-loop-helix (bHLH) proteins, but the mechanism by which these proteins irreversibly commit stem cells to neuronal differentiation is not known. Here we report that expression of the transcription factors Sox1, Sox2 and Sox3 (Sox1-3) is a critical determinant of neurogenesis. Using chick in ovo electroporation, we found that Sox1-3 transcription factors keep neural cells undifferentiated by counteracting the activity of proneural proteins. Conversely, the capacity of proneural bHLH proteins to direct neuronal differentiation critically depends on their ability to suppress Sox1-3 expression in CNS progenitors. These data suggest that the generation of neurons from stem cells depends on the inhibition of Sox1-3 expression by proneural proteins.
Animals; Avian Proteins; Basic Helix-Loop-Helix Transcription Factors; Bromodeoxyuridine/metabolism; Cell Differentiation/physiology; Chick Embryo; DNA-Binding Proteins/metabolism; DNA-Binding Proteins/physiology; Drosophila; Electroporation/methods; Embryonic Induction; Eye Proteins/metabolism; Gene Expression Regulation, Developmental; HMGB Proteins; Helix-Loop-Helix Motifs/physiology; High Mobility Group Proteins/metabolism; High Mobility Group Proteins/physiology; Homeodomain Proteins/metabolism; LIM-Homeodomain Proteins; Membrane Glycoproteins; Mice; Nerve Tissue Proteins/metabolism; Neurofilament Proteins/metabolism; Neurons/metabolism; Neuropeptides/metabolism; Nuclear Proteins/metabolism; Nuclear Proteins/physiology; PAX7 Transcription Factor; Phosphopyruvate Hydratase/metabolism; Proto-Oncogene Proteins c-myc/metabolism; SOXB1 Transcription Factors; Spinal Cord/cytology; Spinal Cord/embryology; Spinal Cord/physiology; Stem Cells; Time Factors; Transcription Factors/metabolism; Tubulin/metabolism; Vertebrates