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.
- Onur Güntürkün
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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
- Heidi Johansen-Berg, University of Oxford, United Kingdom
© 2017, Ocklenburg et al.
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