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Analysis of myelinated axon development in zebrafish

Final Report Summary - ZEBRAFISH MYELIN (Analysis of myelinated axon development in zebrafish)

The majority of axons in our nervous systems are wrapped by a lipid rich structure called the myelin sheath that is made by specialised glial cells. Myelin provides electrical insulation to axons, facilitates rapid energy-efficient nerve conduction, and is essential for long-term nervous system health. Disruption to myelin contributes to the symptoms of numerous devastating conditions, including the demyelinating disease multiple sclerosis, MS. Although our nervous systems have some ability to repair damaged myelin, this process, called remyelination, eventual fails, which leads to the axonal and neuronal degeneration associated with currently untreatable stages of MS. Dr. Lyons’s European Commission International Reintegration project was to perform an “Analysis of myelinated axon development in zebrafish”. Zebrafish are an incredibly powerful model for the study of myelinated axons for several reasons. The small size, optical transparency, relative simplicity, and rapid development of zebrafish embryos, means that biological events can be observed at high resolution as they occur in the living animal. During the period of Dr. Lyons’s International Reintegration Grant, his laboratory generated a suite of transgenic animals to directly visualise and manipulate myelination in the living zebrafish. With these tools they showed that individual axons regulate myelin sheath production by oligodendrocytes, that individual oligodendrocytes generate their myelin sheaths during a very short period of only a few hours and they elucidated how the myelin sheath itself is “wrapped” around those axons. As an indication of the general importance of the laboratory’s reagents, they have shared tools with >40 laboratories worldwide to date.
Zebrafish are also the preeminent vertebrate laboratory model system with which one can carry out large-scale genetic and chemical “screens” to test in a systematic and high-throughput manner how manipulation of different genes or by using chemical compounds can affect biological processes of interest. During his IRG, Dr. Lyons initiated a new genetic screen at the University of Edinburgh and identified new genes required for myelination, and continues to identify more. The group also established platforms to carry out chemical screens to identify chemical compounds that can regulate and promote myelination, with a view to using this information to commence drug development projects for the treatment of diseases such as MS. The work carried out during Dr. Lyons’s IRG lead to numerous new avenues of funding, most recently to the award of long-term funding from the Wellcome Trust, by way of a Senior Research Fellowship in Basic Biomedical Science. Dr. Lyons has also established numerous exciting collaborations, both within the University of Edinburgh and the UK, with prominent European and internationally renowned scientists, and with the major MS drug developer Biogen Idec. Most importantly, during his IRG funding period Dr. Lyons has established a vibrant research group, and has established himself as an internationally recognised leader in the study of myelinated axons.