The ablation of glial fibrillary acidic protein-positive cells from the adult central nervous system results in the loss of forebrain neural stem cells but not retinal stem cells

Eur J Neurosci. 2003 Jul;18(1):76-84. doi: 10.1046/j.1460-9568.2003.02727.x.


The adult mammalian forebrain subependyma contains neural stem cells (NSCs) capable of self-renewal and multilineage differentiation. The in vivo identification of NSCs has not been definitively addressed using a loss of function approach. Using a transgenic mouse expressing herpes-simplex virus thymidine kinase from the glial fibrillary acidic protein (GFAP) promotor, we have selectively killed dividing GFAP-positive cells in the presence of ganciclovir (GCV) and shown a > 95% loss in the numbers of NSCs, as assayed by the formation of clonally derived neurospheres in vitro. This loss is seen following 3 days of GCV exposure in vivo or in vitro only and cannot be rescued by coculturing with pure astrocyte populations or control (green fluorescent protein-expressing) subependymal cells. Exposure to GCV in vitro has no effect on adult retinal stem cells hence, we conclude that adult forebrain NSCs comprise a subpopulation of the GFAP-positive cells within the subependyma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Cell Separation
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / physiology*
  • Cerebral Ventricles / cytology
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Ganciclovir / pharmacology
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / physiology*
  • Immunohistochemistry
  • Mice
  • Mice, Transgenic
  • Neurons / physiology*
  • Prosencephalon / cytology
  • Prosencephalon / physiology*
  • Retina / cytology
  • Retina / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Simplexvirus / enzymology
  • Simplexvirus / genetics
  • Stem Cells / physiology*


  • Antiviral Agents
  • Glial Fibrillary Acidic Protein
  • Ganciclovir