Prof David Lyons

Our current focus is on elucidating mechanisms that orchestrate the formation of myelinated axons, associated with many human diseases including Multiple Sclerosis (MS).

Professor David Lyons

Professor of Neurobiology and Deputy Director (BioQuarter) Centre for Discovery Brain Sciences

Chancellor's Building
49 Little France Crescent
Edinburgh, EH16 4SB

Personal profile

2021- present: Deputy Director (BioQuarter), Centre for Discovery Brain Sciences
2015 - present: Personal Chair of Neurobiology, Centre for Discovery Brain Sciences
2014: Senior Research Fellowship from the Wellcome Trust
2012: Award of a Research Prize from the Lister Institute
2009: joined the Centre for Neuroregeneration through a BBSRC David Phillips Fellowship
2004 - 2009: postdoctoral work at Stanford University in the Department of Developmental Biology with Prof. William Talbot
2003: PhD in Developmental Biology, University College London

Research Theme

Research

We use zebrafish 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 transparent and undergo rapid early development (myelin is formed from just two days after egg 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, make the zebrafish ideal for live in vivo imaging of entire developmental processes. We are currently using these approaches to study cell behaviour and cell-cell interactions during central nervous system myelination in vivo (see Publications below).

We are currently also embarking on a new forward genetic (gene discovery screen), using a transgenic reporter of myelination, to identify the molecular basis of central nervous system (CNS) myelination by oligodendrocytes in vivo, a process about which surprising little is known. In parallel we carrying out chemical compound based screens as an additional approach to identify the molecular basis of CNS myelination, and as part of collaborative drug discovery projects (see Collaborators below).

Funding

Team members

Donia Arafa, PhD Student
Jenea Bin, Research Fellow
Phil Braaker, PhD Student
Maria Eichel-Vogel, Postdoctoral Researcher
Marcus Keatinge, Post-doctoral Fellow
Katy Marshall-Phelps, Research Associate
Edmond Mouofo, PhD Student
Julia Van De Korput, Research Technician

Collaborations

Professor Catherina and Dr. Thomas Becker (CDBS, University of Edinburgh)
Professor Peter Brophy (CDBS, University of Edinburgh)
Professor Jonah Chan (University of California, San Francisco)
Professor Abdel El Manira (Karolinska Institutet, Sweden)
Professor Charles ffrench Constant (CRM, University of Edinburgh)
Professor Robin Franklin (Cambridge University)
Dr. Don Mahad (CCBS, University of Edinburgh)
Dr. Richard Poole (University College London)
Professor Mikael Simons (Max Planck Institute, Goettingen)
Professor William Talbot (Stanford University, USA)
Dr. Claire Wyart (ICM, Paris)
Biogen (Cambridge, MA, USA)

Selected Publications

Madden ME, Suminaite D, Ortiz E, Early JJ, Koudelka S, Livesey MR, Bianco IH, Granato M, Lyons DA. Central nervous system hypomyelination disrupts axonal conduction and behaviour in larval zebrafish. Journal of Neuroscience (2021) Accepted in principle

Almeida RG, Williamson JM, Madden ME, Early JJ, Voas MG, Talbot WS, Bianco IH, Lyons DA. Myelination induces axonal hotspots of synaptic vesicle fusion that promote sheath growth Current Biology (2021) doi: 10.1016/j.cub.2021.06.036

Swire M, Assinck P, McNaughton P, Lyons DA, ffrench-Constant C and Livesey MR Oligodendrocyte HCN2 channels regulate myelin sheath length Journal of Neuroscience (2021) JN-RM-2463-20; DOI: https://doi.org/10.1523/JNEUROSCI.2463-20.2021

Moyon S, Frawley R, Marechal D, Huang D, Marshall-Phelps KLH, Kegel L, Bøstrand SMK, Sadowski B, Jiang YH, Lyons DA, Möbius W, Casaccia P. TET1-mediated DNA hydroxymethylation regulates adult remyelination in mice Nature Communications (2021) 12(1):3359.doi: 10.1038/s41467-021-23735-3

James OG, Selvaraj BT, Magnani D, Burr K, Connick P, Barton SK, Vasistha NA, Hampton DW, Story D, Smigiel R, Ploski R, Brophy PJ, Ffrench-Constant C, Lyons DA, Chandran S iPSC-derived myelinoids to study myelin biology of humans Developmental Cell (2021) 56(9):1346-1358.e6. doi: 10.1016/j.devcel.2021.04.006.

Keatinge M, Tsarouchas TM, Munir T, Porter NJ, Larraz J, Gianni D, Tsai HH, Becker CG, Lyons DA, Becker T. CRISPR gRNA phenotypic screening in zebrafish reveals pro-regenerative genes in spinal cord injury PLoS Genetics (2021) 17(4):e1009515. doi: 10.1371/journal.pgen.1009515.

Campbell JS, Davidson AJ, Todd H, Rodrigues FSLM, Elliot AM, Early JJ, Lyons DA, Feng Y, Wood W. PTPN21/Pez Is a Novel and Evolutionarily Conserved Key Regulator of Inflammation In Vivo Current Biology (20221) 31(4):875-883.e5. doi: 10.1016/j.cub.2020.11.014.

Marshall-Phelps KLH, Kegel L, Baraban M, Ruhwedel T, Almeida RG, Rubio-Brotons M, Klingseisen A, Benito-Kwiecinski S, Early JJ, Bin JM, Suminaite D, Livesey MR, Möbius W, Poole RJ, Lyons DA Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b J Cell Biol (2020) 219 (7): e201909022 LAY ABSTRACT

Licht-Mayer S, Campbell GR, Canizares M, Mehta AR, Gane AB, McGill K, Ghosh A, Fullerton A, Menezes N, Dean J, Dunham J, Al-Azki S, Pryce G, Zandee S, Zhao C, Kipp M, Smith KJ, Baker D, Altmann D, Anderton SM, Kap YS, Laman JD, Hart BA', Rodriguez M, Watzlawick R, Schwab JM, Carter R, Morton N, Zagnoni M, Franklin RJM, Mitchell R, Fleetwood-Walker S, Lyons DA, Chandran S, Lassmann H, Trapp BD, Mahad DJ. Enhanced Axonal Response of Mitochondria to Demyelination Offers Neuroprotection: Implications for Multiple Sclerosis Acta Neuropathol. (2020) Jun 22. doi: 10.1007/s00401-020-02179-x. PMID: 32572598

Klingseisen A, Ristoiu AM, Kegel L, Sherman DL, Rubio-Brotons M, Almeida RG, Koudelka S, Benito-Kwiecinski SK, Poole RJ, Brophy PJ, Lyons DA. Oligodendrocyte Neurofascin Independently Regulates Both Myelin Targeting and Sheath Growth in the CNS. Developmental Cell (2019) 51(6): 730-744

Swire M, Kotelevtsev Y, Webb DJ, Lyons DA, ffrench-Constant C. Endothelin signalling mediates experience-dependent myelination in the CNS eLife (2019) doi: 10.7554/eLife.49493

Harty BL, Coelho F, Pease-Raissi SE, Mogha A, Ackerman SD, Herbert AL, Gereau RW 4th, Golden JP, Lyons DA, Chan JR, Monk KR. Myelinating Schwann cells ensheath multiple axns in the absence of E3 ligase component Fbxw7. Nature Communications. (2019) Jul 5;10(1):2976. doi: 10.1038/s41467-019-10881-y.

Yang Z, Cole KLH, Qiu Y, Somorjai IML, Wijesinghe P, Nylk J, Cochran S, Spalding GC, Lyons DA, Dholakia K. Light sheet microscopy with acoustic sample confinement. Nature Communications. (2019) 10(1):669. doi: 10.1038/s41467-019-08514-5.

Early JJ, Cole KL, Williamson JM, Swire M, Kamadurai H, Muskavitch M, Lyons DA. An automated high-resolution in vivo screen in zebrafish to identify chemical regulators of myelination. eLife (2018) pii: e35136. doi: 10.7554/eLife.35136

Almeida RG, Pan S, Cole KLH, Williamson JM, Early JJ, Czopka T, Klingseisen A, Chan JR, Lyons DA. Myelination of Neuronal Cell bodies when myelin sheaths exceeds axonal demand. Current Biology (2018) doi: 10.1016/j.cub.2018.02.068.

Baraban M, Koudelka S and Lyons DA. Ca2+ activity signatures of myelin sheath formation and growth in vivo. Nature Neuroscience (2018) 21(1):19-23

Karttunen MJ, Czopka T, Goedhart M, Early JJ, Lyons DA. Regeneration of myelin sheaths of normal length and thickness in the zebrafish CNS correlates with growth of axons in caliber. PLoS One (2017) 12(5):e0178058.

Almeida R and Lyons D. Oligodendrocyte Development in the Absence of Their Target Axons In vivo. PLoS ONE (2016) 11(10):e0164432.

Redmond SA, Mei F, Eshed-Eisenbach Y, Osso LA, Leshkowitz D, Shen YA, Kay JN, Aurrand-Lions M, Lyons DA, Peles E, Chan JR. Somatodendritic Expression of JAM2 Inhibits Oligodendrocyte Myelination. Neuron (2016) 91(4):824-36

Koudelka S, Voas MG, Almeida RG, Baraban M, Soetaert J, Meyer MP, Talbot WS and Lyons DA. Individual Neuronal Subtypes Exhibit Diversity in CNS Myelination Mediated by Synaptic Vesicle Release. Current Biology (2016) 26(11):1447-55

Almeida RG and Lyons DA. Intersectional Gene Expression in Zebrafish Using the Split KalTA4 System. Zebrafish (2015) doi:10.1089/zeb.2015.1086

Nawaz S, Sánchez P, Schmitt S, Snaidero N, Mitkovski M, Velte C, Brückner BR, Alexopoulos I, Czopka T, Jung SY, Rhee JS, Janshoff A, Witke W, Schaap IA, Lyons DA, Simons M. Actin Filament Turnover Drives Leading Edge Growth during Myelin Sheath Formation in the Central Nervous System. Developmental Cell (2015) 34(2):139-51

Mensch S, Baraban M, Almeida R, Czopka T, Ausborn J, El Manira A, Lyons DA. Synaptic vesicle release regulates myelin sheath number of individual oligodendrocytes in vivo. Nature Neuroscience (2015) 18(5):628-30

Snaidero N, Möbius W, Czopka T, Hekking LH, Mathisen C, Verkleij D, Goebbels S, Edgar J, Merkler D, Lyons DA, Nave KA, Simons M. Myelin Membrane Wrapping of CNS Axons by PI(3,4,5)P3-Dependent Polarized Growth at the Inner Tongue. Cell. (2014) 156(1-2):277-90.

Czopka, T, ffrench-Constant C, and Lyons DA. Individual oligodendrocytes have only a few hours in which to generate new myelin sheaths in vivo. Developmental Cell (2013) 25(6):599-609.

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