Abstract
The mechanisms by which neural stem cells give rise to neurons, astrocytes, or oligodendrocytes are beginning to be elucidated. However, it is not known how the specification of one cell lineage results in the suppression of alternative fates. We find that in addition to inducing neurogenesis, the bHLH transcription factor neurogenin (Ngn1) inhibits the differentiation of neural stem cells into astrocytes. While Ngn1 promotes neurogenesis by functioning as a transcriptional activator, Ngn1 inhibits astrocyte differentiation by sequestering the CBP-Smad1 transcription complex away from astrocyte differentiation genes, and by inhibiting the activation of STAT transcription factors that are necessary for gliogenesis. Thus, two distinct mechanisms are involved in the activation and suppression of gene expression during cell-fate specification by neurogenin.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Astrocytes / cytology
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Basic Helix-Loop-Helix Transcription Factors
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Blotting, Northern
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Blotting, Western
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Carrier Proteins / metabolism
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Cell Differentiation
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DNA / metabolism
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DNA, Complementary / metabolism
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DNA-Binding Proteins / metabolism
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Immunohistochemistry
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Luciferases / metabolism
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Models, Biological
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Models, Genetic
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Mutagenesis
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Mutation
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Nerve Tissue Proteins / genetics*
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Nerve Tissue Proteins / metabolism*
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Nerve Tissue Proteins / physiology*
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Neuroglia / cytology
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Neuroglia / physiology*
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Neurons / cytology
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Neurons / physiology*
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Nuclear Proteins / metabolism
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Phosphorylation
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Precipitin Tests
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Promoter Regions, Genetic
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Protein Biosynthesis
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Rats
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Rats, Long-Evans
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Signal Transduction
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Smad Proteins
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Smad1 Protein
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Stem Cells / cytology
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Time Factors
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Trans-Activators / metabolism
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Transcription Factors*
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Transcription, Genetic
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Transcriptional Activation
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Transfection
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Xenopus Proteins*
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Carrier Proteins
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DNA, Complementary
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DNA-Binding Proteins
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Nerve Tissue Proteins
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Nuclear Proteins
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Smad Proteins
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Smad1 Protein
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Smad1 protein, rat
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Trans-Activators
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Transcription Factors
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Xenopus Proteins
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citrate-binding transport protein
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neurogenin, Xenopus
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DNA
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Luciferases