title: The co-transduction of Nurr1 and Brn4 genes induces the differentiation of neural stem cells into dopaminergic neurons.
abstract: Fetal brain tissue can be used in cell replacement therapy for PD (Parkinson's disease), but there is a poor donor supply of this tissue. NSCs (neural stem cells) may overcome this problem as they can be isolated and expanded in vitro. However, the usage of NSCs is limited because the differentiation of NSCs into specific dopaminergic neurons has proven difficult. In the present study, we investigated the effect of Nurr1 (nuclear receptor related factor 1), a transcription factor specific for the development and maintenance of the midbrain dopaminergic neurons on inducing the differentiation of NSCs into TH (tyrosine hydroxylase) immunoreactive dopaminergic neurons. Nonetheless, these cells exhibited an immature neuronal morphology with small cell bodies and short neurite processes, and they seldom expressed DAT (dopamine transporter), a late marker of mature dopaminergic neurons. However, forced co-expression of Nurr1 with Brn4, a member of the POU domain family of transcription factors, caused immature Nurr1-induced dopaminergic neurons to differentiate into morphologically and phenotypically more mature neurons. Thus the enriched generation of mature dopaminergic neurons by forced expression of Nurr1 with Brn4 may be of future importance in NSC-based cell replacement therapy for PD.
authors.affiliation: Department of Anatomy and Neurobiology, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Jiangsu Province, Peoples Republic of China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Tan
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Jin
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Tian
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Qin
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui-Xia
authors.initials: HX
authors.lastname: Zhu
authors.forename: Hao-Ming
authors.initials: HM
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000235:genetics*; D050809:POU Domain Factors / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic
chemical_list: D009419:Nerve Tissue Proteins; C539884:Nr4a2 protein, rat; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D050809:POU Domain Factors; C484088:Pou3f4 protein, rat