GDNF promotes neuronal differentiation and dopaminergic development of mouse mesencephalic neurospheres.
In the present study we report establishment of a neurosphere culture system derived from mouse ventral mesencephalon at embryonic day 12 and investigate effects of glial cell line-derived neurotrophic factor (GDNF) in the differentiation potential of the neurospheres. The generated neurospheres exhibit stem cell characteristics, i.e. self-renewal capacity and multipotency. Addition of exogenous GDNF resulted in neural differentiation indicated by reduced number of nestin positive cells. GDNF treatment resulted in increased numbers of beta-III-tubulin immunoreactive cells whereas glial fibrillary acidic protein immunoreactivity was not effected. Most importantly, cell numbers expressing early dopaminergic markers, Nurr1 and Ptx3, were significantly higher in GDNF-treated spheres. We conclude that GDNF promotes differentiation of mouse mesencephalic stem cells towards neuronal lineage and most notably dopaminergic development.
Roussa
Eleni
E
Medical Faculty, Center of the Molecular Physiology of the Brain (CMPB), University Göttingen, Kreuzbergring 36, D-37075 Göttingen, Germany. eroussa@gwdg.de
Krieglstein
Kerstin
K
D000818:Animals; D015415:Biomarkers; D016380:Brain Tissue Transplantation / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D019070:Cell Lineage / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018398:Homeodomain Proteins / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology* / Q000196:embryology; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology*; D019636:Neurodegenerative Diseases / Q000628:therapy; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D015415:Biomarkers; D004268:DNA-Binding Proteins; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018398:Homeodomain Proteins; D009414:Nerve Growth Factors; D009479:Neuropeptides; C539883:Nr4a2 protein, mouse; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; C109467:Ptx3 homeodomain protein, mouse; D014157:Transcription Factors; D014404:Tubulin; D004298:Dopamine