Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany
Judith Schmitz
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany
Zahra Moinfar
Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany
Dirk Moser
Department of Genetic Psychology, Ruhr University Bochum, Bochum, Germany
Rena Klose
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany
Stephanie Lor
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany
Georg Kunz
Department of Obstetrics and Gynecology, St. Johannes Hospital, Dortmund, Germany
Martin Tegenthoff
Department of Neurology, University Hospital Bergmannsheil, Bochum, Germany
Pedro Faustmann
Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany
Clyde Francks
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands
Jörg T Epplen
Department of Human Genetics, Ruhr University Bochum, Bochum, Germany
Robert Kumsta
Department of Genetic Psychology, Ruhr University Bochum, Bochum, Germany
Onur Güntürkün
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany; Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa
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 that 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.
