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Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries
https://elifesciences.org/content/6/e22784
Abstract
The Evolution of Lateralized Brain Circuits
http://journal.frontiersin.org/artic...017.01021/full
Introduction
Update 17/06/2017
https://elifesciences.org/content/6/e22784
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.
The Evolution of Lateralized Brain Circuits
http://journal.frontiersin.org/artic...017.01021/full
In the vast clade of animals known as the bilateria, cerebral and behavioral asymmetries emerge against the backdrop of bilateral symmetry, with a functional trade-off between the two. Asymmetries can lead to more efficient processing and packaging of internal structures, but at the expense of efficient adaptation to a natural world without systematic left-right bias. Asymmetries may arise through the fissioning of ancestral structures that are largely symmetrical, creating new circuits. In humans these may include asymmetrical adaptations to language and manufacture, and as one or other hemisphere gains dominance for functions that were previously represented bilaterally. This is best illustrated in the evolution of such functions as language and tool manufacture in humans, which may derive from the mirror-neuron system in primates, but similar principles probably apply to the many other asymmetries now evident in a wide range of animals. Asymmetries arise in largely independent manner with multi-genetic sources, rather than as a single over-riding principle.
Part of the reason for the fascination with handedness and cerebral asymmetry is that they seem to arise from a system that is for the most part structurally symmetrical, suggesting the operation of some non-material force—and perhaps even encouraging a Cartesian notion of mind over matter (Corballis, 1980). Nevertheless lateral asymmetries can scarcely be understood or even defined except in relation to symmetry. Humans belong to the vast clade of animals known as the bilateria, going back some 550 million years, and characterized by near symmetry about the midsagittal plane. This bilateral symmetry makes us almost indistinguishable from our reflection in the mirror, and may be an adaptation to the fact that for freely moving animals, the natural world is essentially indifferent with respect to left and right. So it is that we have limbs and sense organs arranged in bilateral pairs, and even the brain is more obviously symmetrical than it is asymmetrical. You would be hard-pressed to decide whether a picture of the brain is normal or mirror-reversed, although there are a few small give-away signs.
It is against this fundamentally symmetrical plan that asymmetries sometimes arise, and are of interest. Structural asymmetries are especially evident in the way internal organs are located, with the heart, stomach, and spleen displaced to the left, the liver and gall bladder to the right. Some asymmetries, such as the asymmetrical gallop of a horse, or human preference for one or other hand, are more apparent from function than from structure. This also seems to be true of the human brain, which functions in well-documented asymmetrical ways that are all the more remarkable given its apparent anatomical symmetry.
The pressure toward asymmetry may have to do, at least in part, with packaging and efficiency, especially in internal structures that are largely independent of external constraints. It would simply be inefficient to pack a suitcase while retaining perfect symmetry of its contents; rather, you fit the contents in to make optimal use of the space. Similarly, an automobile retains external symmetry for efficient movement and maneuverability, while its internal parts are asymmetrically organized. Sheer efficiency may therefore have guided the placement of internal bodily organs such as the stomach, which processes food regardless of the manner of its arrival—or its departure. The heart, too, functions internally and is asymmetrical, but retains a degree of symmetry because it must pump blood to both sides of the body.
There is greater pressure for the retention of symmetry in the brain than in the internal organs of the body, because it is involved in coordination of symmetrical actions such as walking or swimming, and the processing of input from symmetrical sense organs. As the brain increases in size and complexity, though, there would be increased demand for asymmetrical packaging, and this pressure would be enhanced by constraints on the size of the skull. This is especially true of bipedal animals, since the demands of upright walking constrains the size of the birth canal, which in turn restricts the size of the head. These constraints conflict with heightened demands for cognitive processing, especially in animals such as humans where survival depends on complex social interactions and the manufacture of tools and habitable environments. In humans, these competing pressures create what has been termed the “obstetrical dilemma,” a hypothesis to explain why childbirth is so difficult, and leads to dangerously early birth normally requiring assistance (Washburn, 1960)—yet we need large brains to cope with the complexities of our lives on the planet. The pressure for larger brains in a constrained skull can also explain why the human brain is exceptionally wrinkled and folded, like an old automobile crushed for infill. The same conflict might also explain why asymmetry seems especially pronounced in the human brain, since reducing redundancy and duplication makes better use of the restricted brain space.
It is against this fundamentally symmetrical plan that asymmetries sometimes arise, and are of interest. Structural asymmetries are especially evident in the way internal organs are located, with the heart, stomach, and spleen displaced to the left, the liver and gall bladder to the right. Some asymmetries, such as the asymmetrical gallop of a horse, or human preference for one or other hand, are more apparent from function than from structure. This also seems to be true of the human brain, which functions in well-documented asymmetrical ways that are all the more remarkable given its apparent anatomical symmetry.
The pressure toward asymmetry may have to do, at least in part, with packaging and efficiency, especially in internal structures that are largely independent of external constraints. It would simply be inefficient to pack a suitcase while retaining perfect symmetry of its contents; rather, you fit the contents in to make optimal use of the space. Similarly, an automobile retains external symmetry for efficient movement and maneuverability, while its internal parts are asymmetrically organized. Sheer efficiency may therefore have guided the placement of internal bodily organs such as the stomach, which processes food regardless of the manner of its arrival—or its departure. The heart, too, functions internally and is asymmetrical, but retains a degree of symmetry because it must pump blood to both sides of the body.
There is greater pressure for the retention of symmetry in the brain than in the internal organs of the body, because it is involved in coordination of symmetrical actions such as walking or swimming, and the processing of input from symmetrical sense organs. As the brain increases in size and complexity, though, there would be increased demand for asymmetrical packaging, and this pressure would be enhanced by constraints on the size of the skull. This is especially true of bipedal animals, since the demands of upright walking constrains the size of the birth canal, which in turn restricts the size of the head. These constraints conflict with heightened demands for cognitive processing, especially in animals such as humans where survival depends on complex social interactions and the manufacture of tools and habitable environments. In humans, these competing pressures create what has been termed the “obstetrical dilemma,” a hypothesis to explain why childbirth is so difficult, and leads to dangerously early birth normally requiring assistance (Washburn, 1960)—yet we need large brains to cope with the complexities of our lives on the planet. The pressure for larger brains in a constrained skull can also explain why the human brain is exceptionally wrinkled and folded, like an old automobile crushed for infill. The same conflict might also explain why asymmetry seems especially pronounced in the human brain, since reducing redundancy and duplication makes better use of the restricted brain space.
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