GDNF augments survival and differentiation of TH-positive neurons in neural progenitor cells.
GDNF plays an important role in the survival and differentiation of primary dopaminergic neurons, but it requires multiple factors for its entire range of activities. This study investigated the effects of GDNF and its cofactors on the development of bFGF-responsive neural progenitor cells (NPCs), mesencephalic and cortical progenitor cells (MP and CP). Various factors were found to have significant inductive effects on the survival and maintenance of these cells in late developmental stages. MP had greater potential than CP to differentiate into dopaminergic neurons. Treatment of NPCs with GDNF and its cofactors enhanced MAP-2 and TH expression, particularly the latter. These findings suggest that NPCs, particularly MP, could develop into more specific neurons if the appropriate factors were applied during the final cell fate specification. They might thus become beneficial sources of donor cells in the treatment of neurological disorders.
Sun
Zhao-hui
ZH
Department of Biological Sciences and Biotechnology, Institute of Neuroscience, Tsinghua University, State Key Laboratory of Biomembranes, Beijing 100084, China.
Lai
Yan-lai
YL
Li
Peng
P
Zuo
Huan-cong
HC
Xie
Zuo-ping
ZP
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D016222:Fibroblast Growth Factor 2; D014446:Tyrosine 3-Monooxygenase; C049301:microtubule-associated protein-2 phosphatase; D010749:Phosphoprotein Phosphatases; D004298:Dopamine