Helios expression coordinates the development of a subset of striatopallidal medium spiny neurons

Author:

Martín-Ibáñez Raquel12345,Pardo Mónica12346,Giralt Albert3478,Miguez Andrés1234,Guardia Inés1234,Marion-Poll Lucile910,Herranz Cristina12345,Esgleas Miriam13411,Barriga Gerardo Garcia-Díaz2347,Edel Michael J.121314,Vicario-Abejón Carlos415,Alberch Jordi23416,Girault Jean-Antoine9,Chan Susan17,Kastner Philippe1718,Canals Josep M.12345ORCID

Affiliation:

1. Stem Cells and Regenerative Medicine Laboratory, University of Barcelona, Barcelona, Spain

2. Neuroscience Institute, University of Barcelona, Barcelona, Spain

3. August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain

4. Networked Biomedical Research Centre for Neurodegenerative Disorders (CIBERNED), Spain

5. Research and Development Unit, Production and validation center of advanced therapies (Creatio), Faculty of Medicine, University of Barcelona, Barcelona, Spain

6. Both authors contributed equally to this work

7. Pathophysiology of Neurodegenerative Diseases Laboratory, Production and validation center of advanced therapies (Creatio), University of Barcelona, Barcelona, Spain

8. Present address: Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin, Paris, France

9. Inserm UMR-S839; Université Pierre et Marie Curie (UPMC, Paris 6), Sorbonne Universités; Institut du Fer à Moulin, Paris, France

10. Present address: Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Mammalian Developmental Epigenetics group, Paris, France

11. Present address: Institute of Stem Cell Research, Helmholtz Center Munich, Munich, Germany

12. Control of Pluripotency Laboratory; Department of Biomedicine, Faculty of Medicine and Health Science, University of Barcelona, Barcelona, Spain

13. Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia

14. School of Medicine and Pharmacology, Anatomy, Physiology and Human Biology, CCTRM, University of Western Australia, Western Australia, Australia

15. Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain

16. Present address: Developmental Neurobiology and Regeneration Group, Department of Cell Biology, University of Barcelona, Barcelona, Spain

17. 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, Illkirch, France

18. Faculté de Médecine, Université de Strasbourg, Strasbourg, France

Abstract

Here we unravel the mechanism of action of 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 that express dopamine 2 receptor (D2R) and enkephalin (ENK). To exert this effect He is expressed in neural progenitor cells (NPCs) retaining them into the G1/G0 phase of the cell cycle. Thus, the lack of He produces 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) that end up dying at postnatal stages. Therefore, He−/- mice show a reduction in the number of Dorso-Medial Striatal MSNs in the adulthood that produces deficits in motor skills acquisition. In addition, overexpression of He in NPCs induce DARPP32 phenotype when transplanted in mouse striatum. Present findings demonstrate that He is involved in the correct development of a subset of striatopallidal MSNs and reveal new cellular mechanisms for neuronal development.

Funder

Ministerio de Economia y Competitividad

Instituto de Salud Carlos III, Ministerio de Economia y Competitividad

Generalitat de Catalunya

CHDI Foundation

Fundació la Marató de TV3

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3