Worm research: Right combination of sugars regulates brain development

Sep. 19, 2013 — If the development of our nervous system is disturbed, we risk developing serious neurological diseases, impairing our sensory systems, movement control or cognitive functions. This is true for all organisms with a well-developed nervous system, from man to worm. New research from BRIC, University of Copenhagen reveals how a tiny molecule called mir-79 regulates neural development in roundworms. The molecule is required for correct migration of specific nerve cells during development and malfunction causes defects in the nervous system of the worm. The research has just been published in the journal Science.

Hundreds of worms lie in a small plastic plate under the laboratory microscope. Over the last three years, the group of Associate Professor Roger Pocock has used the roundworm C. elegans to study the development of the nervous system. They have just made an important discovery.

"Our new results show that a small molecule called mir-79 is indispensable for development of the worm's nervous system. mir-79 acts by equipping special signal molecules with a transmitter, which tells the nerve cells how they should migrate during development of the worm. If we remove mir-79 with gene technology, development of the worm nervous system goes awry," says postdoc Mikael Egebjerg Pedersen, who is responsible for the experimental studies.

Mir-79 adds just the right combination of sugar

The research shows that mir-79 acts by controlling the addition of certain groups of sugars to selected signaling molecules. In the world of cells, sugar molecules act as transmitters.

When the nerve cells come into contact with the sugar-transmitters, they are informed where to locate themselves during neural development. If the researchers remove mir-79, the migration of the nerve cells is misguided causing neuronal defects in the worms.

"It has earlier been shown that signaling molecules guide nerve migration, but our research shows that mir-79 regulates nerve cell migration by controlling the correct balance of sugar-transmitters on signaling molecules. If mir-79 does not function, the worm nervous system is malformed. In the wild, such defects would be harmful for worm survival," says Roger Pocock who leads the research group behind the finding.

Worm studies reveal important clues for neuronal repair

A version of mir-79 called mir-9 is found in humans. Therefore, these results are important for understanding how our nervous system develops during fetal development. In addition, the results add to the understanding of how nerve cells may be stimulated to repair damage in our brain or spinal cord.

"Our nervous system is a tissue which is not easily repaired after damage. So, how certain molecular cues can stimulate nerve cells to migrate is an important brick in the puzzle. This will enable us to understand how nerve tissue can be regenerated after, for example, a stroke or an accident. If we can use such knowledge to mimic the signals, we may be able to stimulate nerve cells to migrate into a damaged area," says Roger Pocock.

Worms are a fantastic model to study how the nervous system develops and how nerve cells form neuronal circuits. Most of the genes that control nervous system development in the worm are also found in humans. At the same time, the reduced complexity of the worm nervous system allows researchers to investigate central biological mechanisms. With new technologies they can mark single cells or molecules, and as worms are transparent, the researchers can track the marked molecules or cells live during worm development.

The next step for the researchers is to investigate how the regulatory pathway they have revealed is regulated in cultures of human cells.

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Genes linked to being right- or left-handed identified

Sep. 12, 2013 — A genetic study has identified a biological process that influences whether we are right handed or left handed.

Scientists at the Universities of Oxford, St Andrews, Bristol and the Max Plank Institute in Nijmegen, the Netherlands, found correlations between handedness and a network of genes involved in establishing left-right asymmetry in developing embryos.

'The genes are involved in the biological process through which an early embryo moves on from being a round ball of cells and becomes a growing organism with an established left and right side,' explained first author William Brandler, a PhD student in the MRC Functional Genomics Unit at Oxford University.

The researchers suggest that the genes may also help establish left-right differences in the brain, which in turn influences handedness.

They report their findings in the open-access journal PLOS Genetics.

Humans are the only species to show such a strong bias in handedness, with around 90% of people being right-handed. The cause of this bias remains largely a mystery.

The researchers, led by Dr Silvia Paracchini at the University of St Andrews, were interested in understanding which genes might have an influence on handedness, in order to gain an insight into the causes and evolution of handedness.

The team carried out a genome-wide association study to identify any common gene variants that might correlate with which hand people prefer using.

The most strongly associated, statistically significant variant with handedness is located in the gene PCSK6, which is involved in the early establishment of left and right in the growing embryo.

The researchers then made full use of knowledge from previous studies of what PCSK6 and similar genes do in mice to reveal more about the biological processes involved.

Disrupting PCSK6 in mice causes 'left-right asymmetry' defects, such as abnormal positioning of organs in the body. They might have a heart and stomach on the right and their liver on the left, for example.

The researchers found that variants in other genes known to cause left-right defects when disrupted in mice were more likely to be associated with relative hand skill than you would expect by chance.

While the team has identified a role for genes involved in establishing left from right in embryo development, William Brandler cautioned that these results do not completely explain the variation in handedness seen among humans. He said: 'As with all aspects of human behaviour, nature and nurture go hand-in-hand. The development of handedness derives from a mixture of genes, environment, and cultural pressure to conform to right-handedness.'

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