Murine embryonic EGF-responsive ventral mesencephalic neurospheres display distinct regional specification and promote survival of dopaminergic neurons

Exp Neurol. 2006 May;199(1):209-21. doi: 10.1016/j.expneurol.2006.02.120. Epub 2006 Apr 19.


Similar to embryonic forebrain, the embryonic mesencephalon contains Fibroblast Growth Factor 2 (FGF2)- and Epidermal Growth Factor (EGF)-responsive progenitors that can be isolated as neurospheres. Developmentally, the FGF2-responsive population appears first and is thought to give rise to EGF-responsive neural stem cells. It is not known whether following this developmental switch of growth factor responsiveness ventral mesencephalic (VM)-derived neural stem cells display distinct region-specific properties. We found that murine VM- and dorsal mesencephalic (DM)-derived primary neurospheres isolated with EGF at embryonic day 14.5 differed with respect to neurosphere formation efficacy and size. VM- but not DM-derived spheres expressed En1, the molecular marker of isthmic organizer, and contained transcripts of BDNF, FGF2, IGF-I and NT-3. Both VM and DM primary neurospheres were self-renewing and gave rise to astroglial cells, but 20% of VM spheres also generated neurons. According to in vitro properties, DM- and majority of VM-derived EGF-responsive progenitors represent glial precursors. VM- but not DM-derived primary neurospheres enriched their respective conditioned medium with factors that promoted the survival of dopaminergic neurons in vitro, suggesting that ventral mesencephalic EGF-responsive progenitors are endowed with the potential to provide trophic support to nearby nascent dopaminergic neurons. These data may have implications in the treatment of Parkinson's disease.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Antigens / metabolism
  • Blotting, Northern / methods
  • Cell Count / methods
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Dopamine / metabolism*
  • Embryo, Mammalian
  • Epidermal Growth Factor / pharmacology*
  • Female
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Mesencephalon / cytology*
  • Mesencephalon / embryology
  • Mice
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects*
  • Neurons / physiology*
  • Pregnancy
  • Proteoglycans / metabolism
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Stem Cells / drug effects*
  • Stem Cells / physiology
  • Time Factors


  • Antigens
  • Culture Media, Conditioned
  • Nerve Tissue Proteins
  • Proteoglycans
  • RNA, Messenger
  • chondroitin sulfate proteoglycan 4
  • Epidermal Growth Factor
  • Dopamine