Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors

Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted... To determine the role of Hes genes in the differentiation process of neuroepithelial (NEP) cells to glial restricted precursor cells (GRPs) and subsequently GRPs to oligodendrocytes and astrocytes, we have examined the effects of Hes1 and Hes5 on glial differentiation. We find that both Hes1 and Hes5 are expressed by GRPs and that Hes1 can drive GRPs to an astrocyte cell fate at the expense of oligodendrocyte differentiation. Overexpression of Hes1 in GRPs results in the up‐regulation of the astrocyte markers glial fibrillary acidic protein and CD44 and the down‐regulation of oligodendrocyte markers myelin proteolipid protein/DM20, GalC, and CNPase. Transcription factors involved in oligodendrocyte differentiation, such as Nkx2.2, Olig1, and Mash1, are also down‐regulated in Hes1‐overexpressing cells. The effect of Hes1 on gliogenesis is stage‐specific as Hes1 does not direct NEP cells to an astrocytic fate. In contrast to Hes1, Hes5 does not promote astrocyte differentiation. Instead, it inhibits both astrocyte and oligodendrocyte differentiation. Overexpression of Notch1 has an effect on gliogenesis similar to that of Hes1 and the mRNA levels of Hes1 are up‐regulated in cells overexpressing Notch1, suggesting that Notch1 could be an upstream activator of Hes1. Developmental Dynamics 675–689, 2003. © 2003 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Developmental Dynamics Wiley

Hes1 but not Hes5 regulates an astrocyte versus oligodendrocyte fate choice in glial restricted precursors

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Publisher
Wiley
Copyright
Copyright © 2003 Wiley‐Liss, Inc.
ISSN
1058-8388
eISSN
1097-0177
DOI
10.1002/dvdy.10278
Publisher site
See Article on Publisher Site

Abstract

To determine the role of Hes genes in the differentiation process of neuroepithelial (NEP) cells to glial restricted precursor cells (GRPs) and subsequently GRPs to oligodendrocytes and astrocytes, we have examined the effects of Hes1 and Hes5 on glial differentiation. We find that both Hes1 and Hes5 are expressed by GRPs and that Hes1 can drive GRPs to an astrocyte cell fate at the expense of oligodendrocyte differentiation. Overexpression of Hes1 in GRPs results in the up‐regulation of the astrocyte markers glial fibrillary acidic protein and CD44 and the down‐regulation of oligodendrocyte markers myelin proteolipid protein/DM20, GalC, and CNPase. Transcription factors involved in oligodendrocyte differentiation, such as Nkx2.2, Olig1, and Mash1, are also down‐regulated in Hes1‐overexpressing cells. The effect of Hes1 on gliogenesis is stage‐specific as Hes1 does not direct NEP cells to an astrocytic fate. In contrast to Hes1, Hes5 does not promote astrocyte differentiation. Instead, it inhibits both astrocyte and oligodendrocyte differentiation. Overexpression of Notch1 has an effect on gliogenesis similar to that of Hes1 and the mRNA levels of Hes1 are up‐regulated in cells overexpressing Notch1, suggesting that Notch1 could be an upstream activator of Hes1. Developmental Dynamics 675–689, 2003. © 2003 Wiley‐Liss, Inc.

Journal

Developmental DynamicsWiley

Published: Apr 1, 2003

References

  • Oh no, Notch again!
    Frisen, Frisen; Lendahl, Lendahl
  • Embryonic‐derived glial‐restricted precursor cells (GRP cells) can differentiate into astrocytes and oligodendrocytes in vivo
    Herrera, Herrera; Yang, Yang; Zhang, Zhang; Proschel, Proschel; Tresco, Tresco; Duncan, Duncan; Luskin, Luskin; Mayer‐Proschel, Mayer‐Proschel
  • Neuroepithelial stem cells from the embryonic spinal cord: isolation, characterization, and clonal analysis
    Kalyani, Kalyani; Hobson, Hobson; Rao, Rao
  • Gliogenesis in the central nervous system
    Lee, Lee; Mayer‐Proschel, Mayer‐Proschel; Rao, Rao
  • A growing family of Notch ligands
    Lendahl, Lendahl
  • Neurogenic genes and vertebrate neurogenesis
    Lewis, Lewis
  • Expression patterns of Jagged, Delta1, Notch1, Notch2, and Notch3 genes identify ligand‐receptor pairs that may function in neural development
    Lindsell, Lindsell; Boulter, Boulter; diSibio, diSibio; Gossler, Gossler; Weinmaster, Weinmaster
  • Hes1 and Hes5 as notch effectors in mammalian neuronal differentiation
    Ohtsuka, Ohtsuka; Ishibashi, Ishibashi; Gradwohl, Gradwohl; Nakanishi, Nakanishi; Guillemot, Guillemot; Kageyama, Kageyama
  • Glial‐restricted precursors are derived from multipotent neuroepithelial stem cells
    Rao, Rao; Mayer‐Proschel, Mayer‐Proschel

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