1. Neuroscience
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Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries

  1. Sebastian Ocklenburg  Is a corresponding author
  2. Judith Schmitz
  3. Zahra Moinfar
  4. Dirk Moser
  5. Rena Klose
  6. Stephanie Lor
  7. Georg Kunz
  8. Martin Tegenthoff
  9. Pedro M Faustmann
  10. Clyde Francks
  11. Jörg T Epplen
  12. Robert Kumsta
  13. Onur Güntürkün
  1. Ruhr University Bochum, Germany
  2. St. Johannes Hospital, Germany
  3. University Hospital Bergmannsheil, Germany
  4. Max Planck Institute for Psycholinguistics, Netherlands
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Cite this article as: eLife 2017;6:e22784 doi: 10.7554/eLife.22784

Abstract

Lateralization is a fundamental principle of nervous system organization but its molecular determinants are mostly unknown. In humans, asymmetric gene expression in the fetal cortex has been suggested as the molecular basis of handedness. However, human fetuses already show considerable asymmetries in arm movements before the motor cortex is functionally linked to the spinal cord, making it more likely that spinal gene expression asymmetries form the molecular basis of handedness. We analyzed genome-wide mRNA expression and DNA methylation in cervical and anterior thoracal spinal cord segments of five human fetuses and show development-dependent gene expression asymmetries. These gene expression asymmetries were epigenetically regulated by miRNA expression asymmetries in the TGF-β signaling pathway and lateralized methylation of CpG islands. Our findings suggest molecular mechanisms for epigenetic regulation within the spinal cord constitute the starting point for handedness, implying a fundamental shift in our understanding of the ontogenesis of hemispheric asymmetries in humans.

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Author details

  1. Sebastian Ocklenburg

    Department of Biopsychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany
    For correspondence
    sebastian.ocklenburg@rub.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5882-3200

  2. Judith Schmitz

    Department of Biopsychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  3. Zahra Moinfar

    Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  4. Dirk Moser

    Department of Genetic Psychology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  5. Rena Klose

    Department of Biopsychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  6. Stephanie Lor

    Department of Biopsychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  7. Georg Kunz

    Department of Obstetrics and Gynecology, St. Johannes Hospital, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.

  8. Martin Tegenthoff

    Department of Neurology, University Hospital Bergmannsheil, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  9. Pedro M Faustmann

    Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  10. Clyde Francks

    Department of Language and Genetics, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands
    Competing interests
    The authors declare that no competing interests exist.

  11. Jörg T Epplen

    Department of Human Genetics, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  12. Robert Kumsta

    Department of Genetic Psychology, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

  13. Onur Güntürkün

    Department of Biopsychology, Institute of Cognitive Neuroscience, Ruhr University Bochum, Bochum, Germany
    Competing interests
    The authors declare that no competing interests exist.

Funding

Deutsche Forschungsgemeinschaft (Gu227/16-1)

  • Onur Güntürkün

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: The study was approved by the Ethics Committee of the Medical Faculty of the Ruhr-University Bochum (registration number 5056-14). All fetal tissue donors signed written informed consent

Reviewing Editor

  1. Heidi Johansen-Berg, University of Oxford, United Kingdom

Publication history

  1. Received: October 29, 2016
  2. Accepted: January 31, 2017
  3. Accepted Manuscript published: February 1, 2017 (version 1)
  4. Version of Record published: February 7, 2017 (version 2)

Copyright

© 2017, Ocklenburg et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

  1. Left or right? Listen to Sebastian Ocklenburg talk about the origins of handedness in animals.

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    Handedness has its origins in the spinal cord.

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