title: 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.
abstract: 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.
authors.affiliation: Department of Surgery, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada. cindi.morsehead@utoronto.ca
authors.forename: Cindi M
authors.initials: CM
authors.lastname: Morshead
authors.forename: A Denize
authors.initials: AD
authors.lastname: Garcia
authors.forename: Michael V
authors.initials: MV
authors.lastname: Sofroniew
authors.forename: Derek
authors.initials: D
authors.lastname: van Der Kooy
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D002552:Cerebral Ventricles / Q000166:cytology; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D015774:Ganciclovir / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D016548:Prosencephalon / Q000166:cytology / Q000502:physiology*; D012160:Retina / Q000166:cytology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013234:Stem Cells / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D005904:Glial Fibrillary Acidic Protein; D015774:Ganciclovir