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

Raquel Martı́n-Ibáñez, Mónica Pardo, Albert Giralt, Andrés Miguez, Inés Guardia, Lucile Marion-Poll, Cristina Herranz, Miriam Esgleas, Gerardo Garcia Dı́az Barriga, Michael J. Edel, Carlos Vicario-Abejón, Jordi Alberch, Jean Antoine Girault, Susan Chan, Philippe Kastner, Josep M. Canals

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    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/G0 phase 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 of He in 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.

    Original languageEnglish
    Pages (from-to)1566-1577
    Number of pages12
    JournalDevelopment (Cambridge)
    Volume144
    Issue number8
    DOIs
    Publication statusPublished - 15 Apr 2017

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