title: Role of Nurr1 in the Generation and Differentiation of Dopaminergic Neurons from Stem Cells.
abstract: NURR1 is an essential transcription factor for the differentiation, maturation, and maintenance of midbrain dopaminergic neurons (DA neurons) as it has been demonstrated using knock-out mice. DA neurons of the substantia nigra pars compacta degenerate in Parkinson's disease (PD) and mutations in the Nurr1 gene have been associated with this human disease. Thus, the study of NURR1 actions in vivo is fundamental to understand the mechanisms of neuron generation and degeneration in the dopaminergic system. Here, we present and discuss findings indicating that NURR1 is a valuable molecular tool for the in vitro generation of DA neurons which could be used for modeling and studying PD in cell culture and in transplantation approaches. Transduction of Nurr1 alone or in combination with other transcription factors such as Foxa2, Ngn2, Ascl1, and Pitx3, induces the generation of DA neurons, which upon transplantation have the capacity to survive and restore motor behavior in animal models of PD. We show that the survival of transplanted neurons is increased when the Nurr1-transduced olfactory bulb stem cells are treated with GDNF. The use of these and other factors with the induced pluripotent stem cell (iPSC)-based technology or the direct reprogramming of astrocytes or fibroblasts into human DA neurons has produced encouraging results for the study of the cellular and molecular mechanisms of neurodegeneration in PD and for the search of new treatments for this disease.
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Rodríguez-Traver
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Oscar
authors.initials: O
authors.lastname: Solís
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Díaz-Guerra
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.
authors.forename: Óscar
authors.initials: Ó
authors.lastname: Ortiz
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Vergaño-Vera
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Héctor R
authors.initials: HR
authors.lastname: Méndez-Gómez
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: García-Sanz
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
authors.affiliation: Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Avenida Doctor Arce 37, 28002, Madrid, Spain. cvicario@cajal.csic.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain. cvicario@cajal.csic.es.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vicario-Abejón
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000502:physiology*; D006801:Humans; D018345:Mice, Knockout; D055495:Neurogenesis / Q000502:physiology*; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology
chemical_list: D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D014157:Transcription Factors
keywords: Differentiation; Dopaminergic neurons; GDNF; NURR1; Parkinson’s disease; Stem cells