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N-CoR controls differentiation of neural stem cells into astrocytes.

Nature | Oct 31, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12410313

Understanding the gene programmes that regulate maintenance and differentiation of neural stem cells is a central question in stem cell biology. Virtually all neural stem cells maintain an undifferentiated state and the capacity to self-renew in response to fibroblast growth factor-2 (FGF2). Here we report that a repressor of transcription, the nuclear receptor co-repressor (N-CoR), is a principal regulator in neural stem cells, as FGF2-treated embryonic cortical progenitors from N-CoR gene-disrupted mice display impaired self-renewal and spontaneous differentiation into astroglia-like cells. Stimulation of wild-type neural stem cells with ciliary neurotrophic factor (CNTF), a differentiation-inducing cytokine, results in phosphatidylinositol-3-OH kinase/Akt1 kinase-dependent phosphorylation of N-CoR, and causes a temporally correlated redistribution of N-CoR to the cytoplasm. We find that this is a critical strategy for cytokine-induced astroglia differentiation and lineage-characteristic gene expression. Recruitment of protein phosphatase-1 to a specific binding site on N-CoR exerts a reciprocal effect on the cellular localization of N-CoR. We propose that repression by N-CoR, modulated by opposing enzymatic activities, is a critical mechanism in neural stem cells that underlies the inhibition of glial differentiation.

Pubmed ID: 12410313 RIS Download

Mesh terms: Animals | Astrocytes | Cell Differentiation | Cell Division | Cell Line | Cell Nucleus | Chromatin | Ciliary Neurotrophic Factor | Cytoplasm | Enzyme Activation | Fibroblast Growth Factor 2 | Humans | Mice | Neurons | Nuclear Proteins | Nuclear Receptor Co-Repressor 1 | Phosphatidylinositol 3-Kinases | Phosphoprotein Phosphatases | Phosphorylation | Protein Phosphatase 1 | Protein Transport | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-akt | Repressor Proteins | Stem Cells

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