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Why are you left or right handed?

One assumption was that differences in gene activity of the right and left hemispheres of the brain are responsible for a person's preference in using either the right or left hand.


How the nervous system organizes itself laterally (along its sides) is still being explored. Patterns of cell movement in the formation of the brain are primarily understood. But, all of the possible genetic influences on cells are still unknown.



Brain cell organization from the proencephalon (forebrain) down to the spinal cord (yellow).
Image Credit: Sopie Stenner, WikiVet.net


According to ultrasound scans done in the 1980s, a visible preference in fetal movement for the left or right hand begins in the eighth week of pregnancy. From the 13th week of pregnancy, a fetus can be seen to suck either right or left thumb. So, a dominant left or right hand is traced back to these early visual references.


However, according to current research, "These results fundamentally change our understanding of the cause of hemispheric asymmetries."


Arm and hand movements are initiated via the motor cortex in a specific region of the cerebral cortex in the human brain. Signals from that area are sent to the spinal cord, which translates it into motion. The motor cortex, however, is not initially connected to the spinal cord, yet even before their connection forms, left or right handedness is visible.

Researchers from the Ruhr University Bochum, and St. Johannes Hospital, and the University Hospital Bergmannsheil, all three in Germany; as well as from the Max Planck Institute for Psycholinguistics, and Radboud University, both in the Netherlands; and finally the Wallenberg Research Centre at Stellenbosch University, South Africa, conducted this research. Their investigation on nerve laterialization is published in the journal eLife.

Comparing gene expression or function, in the spinal cord between the eighth to twelfth week of pregnancy, the researchers detected right-left differences begin in the earlier eighth week.

Movement was detected in the same spinal cord segments controlling arm and leg movements, Brodmann area 4. An unaffiliated research team corroborated asymmetric hand movement also early in fetal development.

Brodmann areas 4
Image Credit:Wellcome Trust Center London, Uk



When the multi-institutional research team traced the cause of asymmetric gene activity, they found epigenetic factors actually appear to influence handedness.


Epigenetic influences come from outside the body's genes (or genome) and are seen as enzymes attached to DNA. Methyl groups wrap tightly around a DNA strand physically compressing it and restricting gene function. They can occur in this instance, and with some variation, on the left or right of the spinal cord. Difference in the attachment location coincides with fetal left or right hand dominance.

Abstract
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.

Authors: 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

Colaborators for the study: Ruhr-Universität Bochum collaborated with the Max Planck Institute for Psycholinguistics in the Netherlands as well as the Dutch Radboud University and the South-African Wellenberg Research Centre at Stellenbosch University.

Funding
The study was funded by the German Research Foundation (Gu227/16-1).

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Twelve week human embryo in utero - rendering.
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