1. Neurogenin promotes neurogenesis and inhibits glial differentiation by independent mechanisms.
- Author
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Sun Y, Nadal-Vicens M, Misono S, Lin MZ, Zubiaga A, Hua X, Fan G, and Greenberg ME
- Subjects
- Animals, Astrocytes cytology, Basic Helix-Loop-Helix Transcription Factors, Blotting, Northern, Blotting, Western, Carrier Proteins metabolism, Cell Differentiation, DNA metabolism, DNA, Complementary metabolism, DNA-Binding Proteins metabolism, Immunohistochemistry, Luciferases metabolism, Models, Biological, Models, Genetic, Mutagenesis, Mutation, Neuroglia cytology, Neurons cytology, Nuclear Proteins metabolism, Phosphorylation, Precipitin Tests, Promoter Regions, Genetic, Protein Biosynthesis, Rats, Rats, Long-Evans, Signal Transduction, Smad Proteins, Smad1 Protein, Stem Cells cytology, Time Factors, Trans-Activators metabolism, Transcription, Genetic, Transcriptional Activation, Transfection, Nerve Tissue Proteins genetics, Nerve Tissue Proteins metabolism, Nerve Tissue Proteins physiology, Neuroglia physiology, Neurons physiology, Transcription Factors, Xenopus Proteins
- 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.
- Published
- 2001
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