Distinct Neural Stem Cells Proliferate in Response to EGF and FGF in the Developing Mouse Telencephalon

Dev Biol. 1999 Apr 1;208(1):166-88. doi: 10.1006/dbio.1998.9192.

Abstract

Multipotent, self-renewing neural stem cells reside in the embryonic mouse telencephalic germinal zone. Using an in vitro neurosphere assay for neural stem cell proliferation, we demonstrate that FGF-responsive neural stem cells are present as early as E8.5 in the anterior neural plate, but EGF-responsive neural stem cells emerge later in development in a temporally and spatially specific manner. By separately blocking EGF and FGF2 signaling, we also show that EGF alone and FGF2 alone can independently elicit neural stem cell proliferation and at relatively high cell densities separate cell nonautonomous effects can substantially enhance the mitogen-induced proliferation. At lower cell densities, neural stem cell proliferation is additive in the presence of EGF and FGF2 combined, revealing two different stem cell populations. However, both FGF-responsive and EGF-responsive neural stem cells retain their self-renewal and multilineage potential, regardless of growth factor conditions. These results support a model in which separate, lineage-related EGF- and FGF-responsive neural stem cells are present in the embryonic telencephalic germinal zone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Division / drug effects
  • Chimera
  • Embryonic and Fetal Development
  • Epidermal Growth Factor / pharmacology*
  • ErbB Receptors / metabolism
  • Fibroblast Growth Factors / pharmacology*
  • Gestational Age
  • Immunohistochemistry
  • Intermediate Filament Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins*
  • Nestin
  • Neurons / metabolism*
  • Ploidies
  • Receptors, Fibroblast Growth Factor / metabolism
  • Signal Transduction / physiology
  • Stem Cells / metabolism*
  • Telencephalon / embryology*

Substances

  • Intermediate Filament Proteins
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • Epidermal Growth Factor
  • ErbB Receptors