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Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state

Author

Listed:
  • R. Patani

    (Anne Mclaren Laboratory for Regenerative Medicine, University of Cambridge
    Cambridge Centre for Brain Repair, University of Cambridge)

  • A. J. Hollins

    (School of Biosciences, Cardiff University)

  • T. M. Wishart

    (Centre for Integrative Physiology, University of Edinburgh
    Euan MacDonald Centre, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.)

  • C. A. Puddifoot

    (Centre for Integrative Physiology, University of Edinburgh
    Euan MacDonald Centre, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.)

  • S. Álvarez

    (Facultade de Química, Universidade de Vigo)

  • A. R. de Lera

    (Facultade de Química, Universidade de Vigo)

  • D. J. A. Wyllie

    (Centre for Integrative Physiology, University of Edinburgh)

  • D. A. S. Compston

    (Cambridge Centre for Brain Repair, University of Cambridge)

  • R. A. Pedersen

    (Anne Mclaren Laboratory for Regenerative Medicine, University of Cambridge)

  • T. H. Gillingwater

    (Centre for Integrative Physiology, University of Edinburgh
    Euan MacDonald Centre, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.)

  • G. E. Hardingham

    (Centre for Integrative Physiology, University of Edinburgh)

  • N. D. Allen

    (School of Biosciences, Cardiff University)

  • S. Chandran

    (Anne Mclaren Laboratory for Regenerative Medicine, University of Cambridge
    Cambridge Centre for Brain Repair, University of Cambridge
    Euan MacDonald Centre, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.)

Abstract

A major challenge in neurobiology is to understand mechanisms underlying human neuronal diversification. Motor neurons (MNs) represent a diverse collection of neuronal subtypes, displaying differential vulnerability in different human neurodegenerative diseases. The ability to manipulate cell subtype diversification is critical to establish accurate, clinically relevant in vitro disease models. Retinoid signalling contributes to caudal precursor specification and subsequent MN subtype diversification. Here we investigate the necessity for retinoic acid in motor neurogenesis from human embryonic stem cells. We show that activin/nodal signalling inhibition, followed by sonic hedgehog agonist treatment, is sufficient for MN precursor specification, which occurs even in the presence of retinoid pathway antagonists. Importantly, precursors mature into HB9/ChAT-expressing functional MNs. Furthermore, retinoid-independent motor neurogenesis results in a ground state biased to caudal, medial motor columnar identities from which a greater retinoid-dependent diversity of MNs, including those of lateral motor columns, can be selectively derived in vitro.

Suggested Citation

  • R. Patani & A. J. Hollins & T. M. Wishart & C. A. Puddifoot & S. Álvarez & A. R. de Lera & D. J. A. Wyllie & D. A. S. Compston & R. A. Pedersen & T. H. Gillingwater & G. E. Hardingham & N. D. Allen & , 2011. "Retinoid-independent motor neurogenesis from human embryonic stem cells reveals a medial columnar ground state," Nature Communications, Nature, vol. 2(1), pages 1-10, September.
    • Handle: RePEc:nat:natcom:v:2:y:2011:i:1:d:10.1038_ncomms1216
    DOI: 10.1038/ncomms1216
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