title: Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons.
abstract: Here, we unravel the mechanism of action of the Ikaros family zinc finger protein Helios (He) during the development of striatal medium spiny neurons (MSNs). He regulates the second wave of striatal neurogenesis involved in the generation of striatopallidal neurons, which express dopamine 2 receptor and enkephalin. To exert this effect, He is expressed in neural progenitor cells (NPCs) keeping them in the G1/G0phase of the cell cycle. Thus, a lack of He results in an increase of S-phase entry and S-phase length of NPCs, which in turn impairs striatal neurogenesis and produces an accumulation of the number of cycling NPCs in the germinal zone (GZ), which end up dying at postnatal stages. Therefore,He-/-mice show a reduction in the number of dorso-medial striatal MSNs in the adult that produces deficits in motor skills acquisition. In addition, overexpression ofHein NPCs induces misexpression of DARPP-32 when transplanted in mouse striatum. These findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.|Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio), Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Martín-Ibáñez
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Pardo
authors.affiliation: August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.|Pathophysiology of Neurodegenerative Diseases Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Giralt
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.
authors.forename: Andrés
authors.initials: A
authors.lastname: Miguez
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: Guardia
authors.affiliation: Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin, 75005 Paris, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Marion-Poll
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.|Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio), Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Herranz
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Esgleas
authors.affiliation: Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.|Pathophysiology of Neurodegenerative Diseases Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Garcia-Díaz Barriga
authors.affiliation: Control of Pluripotency Laboratory, Department of Biomedical Sciences, Faculty of Medicine and Health Science, University of Barcelona, 08036 Barcelona, Spain.|Victor Chang Cardiac Research Institute, Sydney, New South Wales, 2010 Australia.|School of Medicine and Pharmacology, Anatomy, Physiology and Human Biology, CCTRM, University of Western Australia, Western Australia, 6009 Australia.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edel
authors.affiliation: Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.|Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), 28002 Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Vicario-Abejón
authors.affiliation: Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberch
authors.affiliation: Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin, 75005 Paris, France.
authors.forename: Jean-Antoine
authors.initials: JA
authors.lastname: Girault
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Susan
authors.initials: S
authors.lastname: Chan
authors.affiliation: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Inserm U964, Centre National de la Recherche Scientifique (CNRS) UMR 7104, 67400 Illkirch-Graffenstaden, France.|Faculté de Médecine, Université de Strasbourg, 67081 Strasbourg, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Kastner
authors.affiliation: Stem Cells and Regenerative Medicine Laboratory, Production and Validation Center of Advanced Therapies (Creatio), Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain jmcanals@ub.edu.|Neuroscience Institute, University of Barcelona, 08036 Barcelona, Spain.|August Pi i Sunyer Biomedical Research Institute (IDIBAPS), 08036 Barcelona, Spain.|Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain.|Research and Development Unit, Production and Validation Center of Advanced Therapies (Creatio), Faculty of Medicine and Health Sciences, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Josep M
authors.identifier: 0000-0001-6829-7670
authors.initials: JM
authors.lastname: Canals
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D059447:Cell Cycle Checkpoints; D016923:Cell Death; D049109:Cell Proliferation; D003342:Corpus Striatum / Q000166:cytology*; D019927:Cyclin E / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016193:G1 Phase; D005917:Globus Pallidus / Q000166:cytology*; D018345:Mice, Knockout; D009043:Motor Activity; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D016196:S Phase; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D019927:Cyclin E; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C491746:Zfpn1a2 protein, mouse
keywords: Cell cycle; Cell death; Ikaros; Ikzf2; Medium spiny neurons; Neurogenesis