Subject(s)
DNA-Binding Proteins , DNA-Binding Proteins/physiology , Gene Expression Regulation , Mesencephalon/metabolism , Transcription Factors/physiology , Animals , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Nuclear Receptor Subfamily 4, Group A, Member 2 , Parkinson Disease/metabolism , Parkinson Disease/physiopathology , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
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.
