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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/22784 |
| _version_ | 1811227679078219776 |
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| author | Sebastian Ocklenburg Judith Schmitz Zahra Moinfar Dirk Moser Rena Klose Stephanie Lor Georg Kunz Martin Tegenthoff Pedro Faustmann Clyde Francks Jörg T Epplen Robert Kumsta Onur Güntürkün |
| author_facet | Sebastian Ocklenburg Judith Schmitz Zahra Moinfar Dirk Moser Rena Klose Stephanie Lor Georg Kunz Martin Tegenthoff Pedro Faustmann Clyde Francks Jörg T Epplen Robert Kumsta Onur Güntürkün |
| author_sort | Sebastian Ocklenburg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T09:45:58Z |
| format | Article |
| id | doaj.art-ed0869b0503544d2b19345b48ebe75ac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T09:45:58Z |
| publishDate | 2017-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-ed0869b0503544d2b19345b48ebe75ac2022-12-22T03:37:57ZengeLife Sciences Publications LtdeLife2050-084X2017-02-01610.7554/eLife.22784Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetriesSebastian Ocklenburg0https://orcid.org/0000-0001-5882-3200Judith Schmitz1Zahra Moinfar2Dirk Moser3Rena Klose4Stephanie Lor5Georg Kunz6Martin Tegenthoff7Pedro Faustmann8Clyde Francks9Jörg T Epplen10Robert Kumsta11Onur Güntürkün12Institute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, GermanyInstitute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, GermanyDepartment of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, GermanyDepartment of Genetic Psychology, Ruhr University Bochum, Bochum, GermanyInstitute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, GermanyInstitute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, GermanyDepartment of Obstetrics and Gynecology, St. Johannes Hospital, Dortmund, GermanyDepartment of Neurology, University Hospital Bergmannsheil, Bochum, GermanyDepartment of Neuroanatomy and Molecular Brain Research, Ruhr University Bochum, Bochum, GermanyLanguage and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, NetherlandsDepartment of Human Genetics, Ruhr University Bochum, Bochum, GermanyDepartment of Genetic Psychology, Ruhr University Bochum, Bochum, GermanyInstitute of Cognitive Neuroscience, Department Biopsychology, Ruhr University Bochum, Bochum, Germany; Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South AfricaLateralization 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.https://elifesciences.org/articles/22784lateralizationspinal cordepigenetics |
| spellingShingle | Sebastian Ocklenburg Judith Schmitz Zahra Moinfar Dirk Moser Rena Klose Stephanie Lor Georg Kunz Martin Tegenthoff Pedro Faustmann Clyde Francks Jörg T Epplen Robert Kumsta Onur Güntürkün Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries eLife lateralization spinal cord epigenetics |
| title | Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries |
| title_full | Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries |
| title_fullStr | Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries |
| title_full_unstemmed | Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries |
| title_short | Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries |
| title_sort | epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries |
| topic | lateralization spinal cord epigenetics |
| url | https://elifesciences.org/articles/22784 |
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