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Sonic hedgehog and FGF8 collaborate to induce dopaminergic phenotypes in the Nurr1-overexpressing neural stem cell.

Authors
Kim, TE; Lee, HS; Lee, YB; Hong, SH; Lee, YS; Ichinose, H; Kim, SU; Lee, MA
Citation
Biochemical and biophysical research communications, 305(4):1040-1048, 2003
Journal Title
Biochemical and biophysical research communications
ISSN
0006-291X1090-2104
Abstract
Neural stem cells are self-renewing cells capable of differentiating into all neural lineage cells in vivo and in vitro. In the present study, coordinated induction of midbrain dopaminergic phenotypes in an immortalized multipotent neural stem cell line can be achieved by both overexpression of nuclear receptor Nurr1, and fibroblast growth factor-8 (FGF-8), and sonic hedgehog (Shh) signals. Nurr1 overexpression induces neuronal differentiation and confers competence to respond to extrinsic signals such as Shh and FGF-8 that induce dopaminergic fate in a mouse neural stem cell line. Our findings suggest that immortalized NSCs can serve as an excellent model for understanding mechanisms that regulate specification of ventral midbrain DA neurons and as an unlimited source of DA progenitors for treating Parkinson disease patients by cell replacement.
MeSH terms
AnimalsAstrocytes/physiologyCell DifferentiationCell Line, TransformedCoculture TechniquesDNA-Binding Proteins/geneticsDNA-Binding Proteins/metabolism*Dopamine*/biosynthesisFetus/cytologyFibroblast Growth Factor 8Fibroblast Growth Factors/pharmacology*Gene ExpressionHedgehog ProteinsHumansMiceNeurons/cytology*Neurons/enzymologyNuclear Receptor Subfamily 4, Group A, Member 2PhenotypeSignal TransductionStem Cells/cytologyStem Cells/metabolismStem Cells/physiology*Trans-Activators/geneticsTrans-Activators/physiology*Transcription Factors/geneticsTranscription Factors/metabolism*TransfectionTransgenesTyrosine 3-Monooxygenase/analysis
PMID
12767935
Appears in Collections:
Journal Papers > Research Organization > Institute for Medical Sciences
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
AJOU Authors
이, 용범김, 승업이, 명애
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