Most organisms are bilaterally symmetrical – that is, along the longitudinal axis, each half of the body is a mirror image of the other. There are, of course, deviations from this basic body plan, the most obvious being large internal organs such as the heart and liver, which, in mammals, are located on the left and right side of the body, respectively.
Despite some recent advances, very little is known about the developmental mechanisms by which the asymmetries in the nervous system are created. What is known comes mostly from studies of the nematode worm Caenorhabditis elegans, which has a simple nervous system that is amenable to genetic analysis.
The nervous system of the nematode exhibits a large degree of symmetry, in terms of the positions of nerve cell bodies and synapses and the trajectories of nerve fibres. 198 of the 302 cells of the nematode worm nervous system are present in bilaterally symmetrical pairs. However, in the head ganglia there are most of the 75 cells of which the ventral nerve cord is composed have axons that project along the right side of the body.
As well as these anatomical differences, the nervous system of the nematode worm exhibits functional asymmetries. For example, the taste receptor neurons ASEL (on the left) and ASER (on the right) sense distinct classes of water-soluble chemicals. In the cells, members of a family of genes encoding putative taste receptor genes are expressed asymmetrically.
Another well-characterized asymmetry in the nematode occurs in the oflactory system. Olfactory neurons AWCL and ACWR are mirror images of each other, but only one of them expresses the str-2 gene, which encodes a G protein-coupled olfactory receptor. The other cell in the pair expresses a different receptor; together, the two neurons enable the worm to discriminate between two coincinding odours.
Whereas the expression pattern of the taste receptors is genetically predetermined, that of the olfactory receptors is down to chance. Half of the worms in any given population express str-2 on the left, and the other half express the gene on the right. The “decision” as to which one expresses str-2, and which one expresses another receptor, is determined by a signalling event that occurs between the two cells – which are in contact with each other – during development.
Most of the cells in the nematode nervous system are derived from the AB founder cell. The first time this cell divides, it does so along the left-right axis of the embryo, but all subsequent cell divisions occur along the antero-posterior (or front-to-back) axis.
Exactly how laterality is generated in the nematode remains unclear, but research published recently suggests that asymmetry is generated soon after fertilization – at the 6-cell stage, or perhaps even earlier. It is thought that some kind of asymmetric pattern is laid down at around the time of the AB founder cell’s second division.
Laterality in the humble worm is directly relevant to humans. It has long been known that certain cognitive functions are localized to one or the other cerebral hemispheres. The processing of speech is the best known example of localization of cerebral function. From the work carried out in the 1860s by Paul Broca and Carl Wernicke, we know that the brain’s speech centres are located predominantly in the temporal lobe of the left hemisphere.
Because it contains the speech centres (which are now usually called Broca’s and Wernicke’s areas), the left hemisphere is said to be ‘dominant’. Related to cerebral dominance is handedness. 90% of people are right-handed, and have speech localized to the left hemisphere. Some left-handed people have a bilateral representation of speech; in others, speech is predominantly processed in the right hemisphere.
Associated with these functional and behavioural asymmetries are anatomical ones – the temporal lobe is slightly larger on the left than on the right, because it accomodates speech centres that are enlarged. It appears that the human brain is already asymmetrical before birth. At 7 weeks after fertilization, the right hand of a human foetus is more developed than the left. Neuroimaging studies show that the temporal lobes are already asymmetrical from 10 weeks onwards, and that maturation of the left hemisphere precedes tha of the right between 1-3 years of age (around the time of language development).
In people with the rare congenital condition inversus totalis, the laterality of the visceral organs are reversed. The heart, stomach and spleen are on the right, and the liver is on the left. However, the speech centres in people with inversus totalis are still found in the left hemisphere of the brain, and their handedness is unaffected. This suggests that the mechanisms that generate asymmetries in the brain are independent of those that do so in the the rest of the body.
Asymmetries can be advantageous. The asymmetrical olfactory and gustatory system of C. elegans, for example, enable the worm to detect twice as many odours and tastes. In humans, laterality and asymmetry is likely to have evolved because of social factors – it would have been beneficial to have the same asymmetries as others. (By contrast, handedness in mice, cats and dogs is random – about half are “left-pawed” and the other half are “right-pawed”.)
A study published last month provides some evidence of a social influence on handedness. Chris McManus and Alex Hartigan analysed documentary films produced at the beginning of the 20th century. Out of nearly 400 individuals who were observed waving their hands in the film footage, only 3% waved their left hands. Today, about 11% of the population is left-handed.
Lateralization evolved in bilateral organisms at least 500 million years ago. One study showed that there was a bias for trilobites to incur injuries on one side, suggesting that these ancient arthropods – which became extinct some 250 million years ago – preferred one direction to another when escaping from predators (or, alternatively, that their predators preferred to attack from one direction).
But it is unclear whether the evolutionary ancestor of all bilateral organisms are derived was itself lateralized or perfectly symmetrical. If it was perfectly symmetrical, then the lateralizations we see today would have been superimposed upon the ancestral body plan at some point in evolution.