GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain

Nat Neurosci. 2004 Nov;7(11):1233-41. doi: 10.1038/nn1340. Epub 2004 Oct 24.

Abstract

Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analysis of Variance
  • Animals
  • Bromodeoxyuridine / metabolism
  • Cell Count / methods
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Size
  • Ganciclovir / pharmacology
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Glial Fibrillary Acidic Protein / genetics
  • Glial Fibrillary Acidic Protein / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Immunohistochemistry / methods
  • Integrases / metabolism
  • Mice
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neuroglia / physiology*
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Olfactory Bulb / cytology
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / metabolism
  • Phosphopyruvate Hydratase / metabolism
  • Prosencephalon / cytology*
  • Prosencephalon / drug effects
  • Prosencephalon / physiology
  • Sialic Acids / metabolism
  • Stem Cells / drug effects
  • Stem Cells / physiology*
  • Thymidine Kinase / genetics
  • Tubulin / metabolism
  • beta-Galactosidase / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Microtubule-Associated Proteins
  • Neural Cell Adhesion Molecule L1
  • Neuropeptides
  • Sialic Acids
  • Tubulin
  • beta3 tubulin, mouse
  • doublecortin protein
  • polysialyl neural cell adhesion molecule
  • Green Fluorescent Proteins
  • Thymidine Kinase
  • Cre recombinase
  • Integrases
  • beta-Galactosidase
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine
  • Ganciclovir