Murine embryonic EGF-responsive ventral mesencephalic neurospheres display distinct regional specification and promote survival of dopaminergic neurons.
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.
Moses
David
D
Howard Florey Institute of Experimental Physiology and Medicine, The University of Melbourne, Victoria 3010, Australia.
Teper
Yaroslav
Y
Gantois
Ilse
I
Finkelstein
David I
DI
Horne
Malcolm K
MK
Drago
John
J
D000367:Age Factors; D000818:Animals; D000941:Antigens / Q000378:metabolism; D015152:Blotting, Northern / Q000379:methods; D002452:Cell Count / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004622:Embryo, Mammalian; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D017077:Culture Media, Conditioned; D004298:Dopamine; D004815:Epidermal Growth Factor; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D000099216:Chondroitin Sulfate Proteoglycan 4