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Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors

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  • Serafí Cambray

    (British Heart Foundation Centre of Research Excellence, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus
    Stem cell Neurogenesis Group, Epigenetics Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Charles Arber

    (Stem cell Neurogenesis Group, Epigenetics Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Graham Little

    (Neuroplasticity and Disease Group, Genes and Metabolism Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Antonios G. Dougalis

    (Neurophysiology Group, Genes and Metabolism Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Vincenzo de Paola

    (Neuroplasticity and Disease Group, Genes and Metabolism Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Mark A. Ungless

    (Neurophysiology Group, Genes and Metabolism Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Meng Li

    (Stem cell Neurogenesis Group, Epigenetics Section, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus)

  • Tristan A. Rodríguez

    (British Heart Foundation Centre of Research Excellence, National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus)

Abstract

Understanding the mechanisms underlying neural progenitor differentiation and neuronal fate specification is critical for the use of embryonic stem cells (ESCs) for regenerative medicine. Cortical interneurons are of particular interest for cell transplantation; however, only a limited subset of these neurons can be generated from ESCs. Here we uncover a pivotal role for Activin in regulating the differentiation and identity of telencephalic neural precursors derived from mouse and human ESCs. We show that Activin directly inhibits the mitogenic sonic hedgehog pathway in a Gli3-dependent manner while enhancing retinoic acid signalling, the pro-neurogenic pathway. In addition, we demonstrate that Activin provides telencephalic neural precursors with positional cues that specifically promote the acquisition of a calretinin interneuron fate by controlling the expression of genes that regulate cortical interneuron identity. This work demonstrates a novel means for regulating neuronal differentiation and specification of subtype identity.

Suggested Citation

  • Serafí Cambray & Charles Arber & Graham Little & Antonios G. Dougalis & Vincenzo de Paola & Mark A. Ungless & Meng Li & Tristan A. Rodríguez, 2012. "Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors," Nature Communications, Nature, vol. 3(1), pages 1-11, January.
    • Handle: RePEc:nat:natcom:v:3:y:2012:i:1:d:10.1038_ncomms1817
    DOI: 10.1038/ncomms1817
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