Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries.
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.
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany.
Sebastian
0000-0001-5882-3200
S
Ocklenburg
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany.
Judith
J
Schmitz
Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany.
Zahra
Z
Moinfar
Department of Genetic Psychology, Ruhr University Bochum, Bochum, Germany.
Dirk
D
Moser
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany.
Rena
R
Klose
Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany.
Stephanie
S
Lor
Department of Obstetrics and Gynecology, St. Johannes Hospital, Dortmund, Germany.
Georg
G
Kunz
Department of Neurology, University Hospital Bergmannsheil, Bochum, Germany.
Martin
M
Tegenthoff
Department of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, Germany.
Pedro
P
Faustmann
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands.|Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, Netherlands.
Clyde
C
Francks
Department of Human Genetics, Ruhr University Bochum, Bochum, Germany.
Jörg T
JT
Epplen
Department of Genetic Psychology, Ruhr University Bochum, Bochum, Germany.
Robert
R
Kumsta
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.
Onur
O
Güntürkün
D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D007839:Functional Laterality; D020869:Gene Expression Profiling; D006801:Humans; D035683:MicroRNAs / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D035683:MicroRNAs; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta
epigenetics; human; lateralization; neuroscience; spinal cord