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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...

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Autores principales: Ocklenburg, Sebastian, Schmitz, Judith, Moinfar, Zahra, Moser, Dirk, Klose, Rena, Lor, Stephanie, Kunz, Georg, Tegenthoff, Martin, Faustmann, Pedro, Francks, Clyde, Epplen, Jörg T, Kumsta, Robert, Güntürkün, Onur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295814/
https://www.ncbi.nlm.nih.gov/pubmed/28145864
http://dx.doi.org/10.7554/eLife.22784
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author Ocklenburg, Sebastian
Schmitz, Judith
Moinfar, Zahra
Moser, Dirk
Klose, Rena
Lor, Stephanie
Kunz, Georg
Tegenthoff, Martin
Faustmann, Pedro
Francks, Clyde
Epplen, Jörg T
Kumsta, Robert
Güntürkün, Onur
author_facet Ocklenburg, Sebastian
Schmitz, Judith
Moinfar, Zahra
Moser, Dirk
Klose, Rena
Lor, Stephanie
Kunz, Georg
Tegenthoff, Martin
Faustmann, Pedro
Francks, Clyde
Epplen, Jörg T
Kumsta, Robert
Güntürkün, Onur
author_sort Ocklenburg, Sebastian
collection PubMed
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. DOI: http://dx.doi.org/10.7554/eLife.22784.001
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spelling pubmed-52958142017-02-10 Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries Ocklenburg, Sebastian Schmitz, Judith Moinfar, Zahra Moser, Dirk Klose, Rena Lor, Stephanie Kunz, Georg Tegenthoff, Martin Faustmann, Pedro Francks, Clyde Epplen, Jörg T Kumsta, Robert Güntürkün, Onur eLife Neuroscience 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. DOI: http://dx.doi.org/10.7554/eLife.22784.001 eLife Sciences Publications, Ltd 2017-02-01 /pmc/articles/PMC5295814/ /pubmed/28145864 http://dx.doi.org/10.7554/eLife.22784 Text en © 2017, Ocklenburg et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Ocklenburg, Sebastian
Schmitz, Judith
Moinfar, Zahra
Moser, Dirk
Klose, Rena
Lor, Stephanie
Kunz, Georg
Tegenthoff, Martin
Faustmann, Pedro
Francks, Clyde
Epplen, Jörg T
Kumsta, Robert
Güntürkün, Onur
Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries
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 Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5295814/
https://www.ncbi.nlm.nih.gov/pubmed/28145864
http://dx.doi.org/10.7554/eLife.22784
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