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Dr David Lyons
BBSRC David Phillips Fellow
Chancellor's Building
University of Edinburgh
49 Little France Crescent
Edinburgh
EH16 4SB
Telephone: +44 (0) 131 242 7986
Fax: +44 (0) 131 242 7987
Email: david.lyons@ed.ac.uk
2011 European Zebrafish Meeting: www.zebrafish2011.org
Biographical Profile
David Lyons received his B.Sc. (Neuroscience, 1999) and Ph.D. (Developmental Biology, 2003) from University College London. He then undertook postdoctoral work at Stanford University in the Department of Developmental Biology with Prof. William Talbot (2004-2009). In 2009, Dr. Lyons joined the Centre for Neuroregeneration.
Research Overview
We use the zebrafish embryo as a model organism to dissect the molecular and cellular basis of nervous system development. Our current focus is on elucidating mechanisms that orchestrate the formation of myelinated axons. Myelinated axons are essential for normal nervous system development and function, and disruption of the myelin sheath and associated axons is associated with many human diseases including Multiple Sclerosis (MS).
Our lab uses zebrafish for two principle reasons, their amenability for live cell imaging and high-resolution cellular analyses, and their ability to be used to carry out large-scale genetic and chemical screens.
Zebrafish embryos are beautifully transparent and undergo relatively rapid early development (myelin is formed from just two days post fertilization). These facts coupled with the relative simplicity of the early nervous system and the availability of transgenic lines that drive fluorescent reporters in a variety of cell types and activity states, make the zebrafish ideal for live in vivo imaging of entire developmental processes, which we are currently using to elucidate cell behaviour of myelination in vivo. We also aim to ultimately reconstruct molecular and cellular aspects of myelinated axon formation at super and ultrastructural resolution.
In a forward genetic screen carried out in Will Talbot’s lab at Stanford University we identified ten genes with essential functions in the development of myelinated axons in zebrafish. We identified new roles for genes already implicated in myelinating glial cell development as well as key roles for novel genes with no previously characterized role in myelination (see publications). Our genetic screen also isolated mutations in the zebrafish homologues of four human disease genes, giving the possibility of establishing zebrafish models of important diseases of myelinated axons. Although this genetic screen represented an important step in establishing the zebrafish as a relevant organism with which to dissect myelination, future work will continue to identify new genes essential to the formation and function of myelinated axons.
In collaboration with the laboratory of Prof. Manfred Auer (University of Edinburgh, formerly Executive Director of Innovative Screening Technologies, Novartis), we are establishing platforms to carry out high-throughput chemical screening using zebrafish. Zebrafish embryos represent an almost ideal system for in vivo chemical screens, due to their small size, rapid development, aquatic existence, and profound molecular, cellular, and systemic similarity to higher vertebrates, including humans. Through this collaboration, we hope to use chemical systems biological approaches to identify new molecules involved in specific biological processes, and contribute to lead identification and analysis stages of drug discovery.
Group Members
Collaborators
Funding
Our work is funded by the BBSRC, the European Commission and the UK Multiple Sclerosis Society.
Selected Recent Publications
Raphael AR, Lyons DA and Talbot WS.
ErbB signaling has a role in radial sorting independent of Schwann cell number.
Glia (2011) 59:1047-55
Almeida RG, Czopka, T, ffrench-Constant C, and Lyons DA.
Individual axons regulate the myelinating potential of single oligodendrocytes in vivo.
Development (2011) 138:4443-4450
Czopka T and Lyons DA.
Dissecting Mechanisms of Myelinated Axon formation Using Zebrafish.
Methods in Cell Biology(2011) 105: 25-62
Lyons DA, Naylor SG, Scholze, and Talbot WS.
Kif1b is essential for mRNA localization in oligodendrocytes and development of myelinated axons.
Nature Genetics. (2009) 41: 854-858
Lyons DA, Naylor SG, Mercurio S, Dominguez C, and Talbot WS.
KBP is essential for axonal structure, outgrowth, and maintenance in zebrafish, providing insight into the cellular basis of Goldberg-Shprintzen syndrome
Development. (2008) 135: 599-608
Tawk M, Araya C, Lyons DA, Reugels AM, Girdler GC, Bayley PR, Hyde DR, Tada M and Clarke JD.
A mirror-symmetric cell division that orchestrates neuroepithelial morphogenesis.
Nature (2007) 446: 797-800
Voas MG, Lyons DA, Naylor SG, Arana N, Rasband MN and Talbot WS.
alphaII-Spectrin Is Essential for Assembly of the Nodes of Ranvier in Myelinated Axons.
Current Biology (2007) 17: 562-8.
Pogoda HM, Sternheim N, Lyons DA, Diamond B, Hawkins TA, Woods IG, Bhatt DH, Franzini-Armstrong C, Dominguez C, Arana N, Jacobs J, Nix R, Fetcho JR,and Talbot WS.
A genetic screen identifies genes essential for development of myelinated axons in zebrafish.
Developmental Biology (2006) 298(1):118-31.
Woods IG, Lyons DA, Voas MG, Pogoda HM and Talbot WS.
nsf is essential for organization of myelinated axons in zebrafish.
Current Biology (2006) 16: 636-48.
Lyons DA, Pogoda HM, Voas MG, Woods IG, Diamond B, Nix R, Arana N, Jacobs J, and Talbot WS.
erbb3 and erbb2 are essential for Schwann cell migration and myelination in zebrafish.
Current Biology (2005) 15: 513-524.
Review
Lyons DA and Talbot WS.
Axonal domains: role for paranodal junction in node of Ranvier assembly.
Current Biology (2008) 18:R876-9.
Key Earlier Publications
Lyons DA, Guy AT and Clarke JDW.
Monitoring neural progenitor fate through multiple rounds of division in an intact vertebrate brain.
Development (2003) 130: 3427-3436.