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N-CoR controls differentiation of neural stem cells into astrocytes

Author

Listed:
  • Ola Hermanson

    (University of California, San Diego, School of Medicine
    Medical Nobel Institute, Karolinska Institute)

  • Kristen Jepsen

    (University of California, San Diego, School of Medicine)

  • Michael G. Rosenfeld

    (University of California, San Diego, School of Medicine)

Abstract

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)1,2,3,4,5. 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 cytokine3, 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.

Suggested Citation

  • Ola Hermanson & Kristen Jepsen & Michael G. Rosenfeld, 2002. "N-CoR controls differentiation of neural stem cells into astrocytes," Nature, Nature, vol. 419(6910), pages 934-939, October.
    • Handle: RePEc:nat:nature:v:419:y:2002:i:6910:d:10.1038_nature01156
    DOI: 10.1038/nature01156
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    Cited by:

    1. Benjamin A. Nacev & Francisco Sanchez-Vega & Shaleigh A. Smith & Cristina R. Antonescu & Evan Rosenbaum & Hongyu Shi & Cerise Tang & Nicholas D. Socci & Satshil Rana & Rodrigo Gularte-Mérida & Ahmet Z, 2022. "Clinical sequencing of soft tissue and bone sarcomas delineates diverse genomic landscapes and potential therapeutic targets," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Andreas Lackner & Michael Müller & Magdalena Gamperl & Delyana Stoeva & Olivia Langmann & Henrieta Papuchova & Elisabeth Roitinger & Gerhard Dürnberger & Richard Imre & Karl Mechtler & Paulina A. Lato, 2023. "The Fgf/Erf/NCoR1/2 repressive axis controls trophoblast cell fate," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Min Yan Shi & Hwang Chan Yu & Chang Yeob Han & In Hyuk Bang & Ho Sung Park & Kyu Yun Jang & Sangkyu Lee & Jeong Bum Son & Nam Doo Kim & Byung-Hyun Park & Eun Ju Bae, 2023. "p21-activated kinase 4 suppresses fatty acid β-oxidation and ketogenesis by phosphorylating NCoR1," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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