EGF-induced expansion of migratory cells in the rostral migratory stream

PLoS One. 2012;7(9):e46380. doi: 10.1371/journal.pone.0046380. Epub 2012 Sep 28.

Abstract

The presence of neural stem cells in the adult brain is currently widely accepted and efforts are made to harness the regenerative potential of these cells. The dentate gyrus of the hippocampal formation, and the subventricular zone (SVZ) of the anterior lateral ventricles, are considered the main loci of adult neurogenesis. The rostral migratory stream (RMS) is the structure funneling SVZ progenitor cells through the forebrain to their final destination in the olfactory bulb. Moreover, extensive proliferation occurs in the RMS. Some evidence suggest the presence of stem cells in the RMS, but these cells are few and possibly of limited differentiation potential. We have recently demonstrated the specific expression of the cytoskeleton linker protein radixin in neuroblasts in the RMS and in oligodendrocyte progenitors throughout the brain. These cell populations are greatly altered after intracerebroventricular infusion of epidermal growth factor (EGF). In the current study we investigate the effect of EGF infusion on the rat RMS. We describe a specific increase of radixin(+)/Olig2(+) cells in the RMS. Negative for NG2 and CNPase, these radixin(+)/Olig2(+) cells are distinct from typical oligodendrocyte progenitors. The expanded Olig2(+) population responds rapidly to EGF and proliferates after only 24 hours along the entire RMS, suggesting local activation by EGF throughout the RMS rather than migration from the SVZ. In addition, the radixin(+)/Olig2(+) progenitors assemble in chains in vivo and migrate in chains in explant cultures, suggesting that they possess migratory properties within the RMS. In summary, these results provide insight into the adaptive capacity of the RMS and point to an additional stem cell source for future brain repair strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Epidermal Growth Factor / administration & dosage*
  • Gene Expression / drug effects
  • Injections, Intraventricular
  • Intralaminar Thalamic Nuclei / cytology
  • Intralaminar Thalamic Nuclei / drug effects*
  • Intralaminar Thalamic Nuclei / physiology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism*
  • Neurogenesis / drug effects
  • Neurogenesis / physiology*
  • Olfactory Bulb / cytology
  • Olfactory Bulb / drug effects
  • Olfactory Bulb / physiology
  • Oligodendrocyte Transcription Factor 2
  • Rats
  • Rats, Wistar

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Olig2 protein, rat
  • Oligodendrocyte Transcription Factor 2
  • radixin
  • Epidermal Growth Factor

Grants and funding

This work was supported by grants from the Swedish Medical Research Council (VR-M 2011-3113), the Swedish Childhood Cancer Foundation (PROJ10/044 and NBCNSDoktBidr09/007, Västra Götaland regional funds for biomedical research (ALFGBG-146341), The Swedish Parkinson's Disease Association, Stiftelsen Wilhelm och Martina Lundgrens Vetenskapsfond, Rune oct Ulla Amlövs Stiftelse, Stiftelsen Edit Jacobsons Donationsfond and Stroke-Riksförbundet. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.