Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries
- Ruhr University Bochum, Germany
- St. Johannes Hospital, Germany
- University Hospital Bergmannsheil, Germany
- Max Planck Institute for Psycholinguistics, Netherlands
- Cited 41
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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.
Article and author information
Author details
Sebastian Ocklenburg
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
- Heidi Johansen-Berg, University of Oxford, United Kingdom
Publication history
- Received: October 29, 2016
- Accepted: January 31, 2017
- Accepted Manuscript published: February 1, 2017 (version 1)
- 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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