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Prof William Richardson

Research Summary

We study the biology of CNS stem cells and their neuronal and glial progeny, in order to better understand their roles in normal CNS physiology. Stem cells in the adult forebrain generate new neurons for the olfactory bulb and hippocampus throughout life. The role of these adult-born neurons is not clear, although they appear to be involved in some aspects of olfactory and spatial memory function. Another population of stem-like cells - known as NG2 cells - is distributed uniformly throughout the brain and spinal cord. These generate many new oligodendrocytes during adult life, raising the intriguing possibility that late-forming myelin might modify the properties of neural circuits and contribute to neural plasticity. We found recently that NG2 cells also generate small numbers of projection neurons in the piriform cortex (primary olfactory cortex), raising further questions about adult neurogenesis and its potential role in plasticity. With collaborators at UCL and in the USA, we are also investigating the development of CNS glial cells (oligodendrocytes and astrocytes) and their interactions with one another and with neurons. We specialize in the use of transgenic mouse technology to manipulate cells of interest in vivo. We also use chick, zebrafish and cell culture models where appropriate.

Research Activities

  • Axonal regeneration
  • Development and evolution of novel traits including vertebrate myelin and diopsid eyestalks
  • Neuron-glial interactions
  • Properties and functions of neural stem cells and their progeny in the embryonic and postnatal CNS.

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. Philips T,Bento-Abreu A,Nonneman A,Haeck W,Staats K,Geelen V,Hersmus N,Küsters B,Van Den Bosch L,Van Damme P,Richardson WD,Robberecht W (2013) Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis Brain, 136(2), 471 - 482.
  2. Young KM,Psachoulia K,Tripathi RB,Dunn SJ,Cossell L,Attwell D,Tohyama K,Richardson WD (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodeling. Neuron, 77(5), 873 - 885. 10.1016/j.neuron.2013.01.006.
  3. Taveira-Marques R,Holz A,Tsai H-H,Arnold H-H,Rowitch DH,Kessaris N,Richardson WD (2013) Separate progenitors for somatic and visceral motor neurons in mouse spinal cord., In preparation.
  4. Tsai HH,Li H,Fuentealba LC,Molofsky AV,Taveira-Marques R,Zhuang H,Tenney A,Murnen AT,Fancy SP,Merkle F,Kessaris N,Alvarez-Buylla A,Richardson WD,Rowitch DH (2012) Regional astrocyte allocation regulates CNS synaptogenesis and repair. Science, 337(6092), 358 - 362. 10.1126/science.1222381.
  5. Hari L,Miescher I,Shakhova O,Suter U,Chin L,Taketo M,Richardson WD,Kessaris N,Sommer L (2012) Temporal control of neural crest lineage generation by wnt/β-catenin signaling Development (Cambridge), 139(12), 2107 - 2117.
  6. Molofsky AV,Krenick R,Ullian E,Tsai H-H,Deneen B,Richardson WD,Barres BA,Rowitch DH (2012) Astrocytes and disease: a neurodevelopmental perspective GENES & DEVELOPMENT, 26(9), 891 - 907. 10.1101/gad.188326.112.
  7. Clarke LE,Young KM,Hamilton NB,Li H,Richardson WD,Attwell D (2012) Properties and fate of oligodendrocyte progenitor cells in the corpus callosum, motor cortex, and piriform cortex of the mouse. J Neurosci, 32(24), 8173 - 8185. 10.1523/JNEUROSCI.0928-12.2012.
  8. Chittka A,Nitarska J,Grazini U,Richardson WD (2012) Transcription factor positive regulatory domain 4 (PRDM4) recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation. J Biol Chem, 287(51), 42995 - 43006. 10.1074/jbc.M112.392746.
  9. Anttonen T,Kirjavainen A,Belevich I,Laos M,Richardson WD,Jokitalo E,Brakebusch C,Pirvola U (2012) Cdc42-dependent structural development of auditory supporting cells is required for wound healing at adulthood Scientific Reports, 2.
  10. Tripathi RB,Clarke LE,Burzomato V,Kessaris N,Anderson PN,Attwell D,Richardson WD (2011) Dorsally and ventrally derived oligodendrocytes have similar electrical properties but myelinate preferred tracts. J Neurosci, 31(18), 6809 - 6819. 10.1523/JNEUROSCI.6474-10.2011.
  11. Richardson WD,Young KM,Tripathi RB,McKenzie I (2011) NG2-glia as multipotent neural stem cells: fact or fantasy? Neuron, 70(4), 661 - 673. 10.1016/j.neuron.2011.05.013.
  12. Li H,de Faria JP,Andrew P,Nitarska J,Richardson WD (2011) Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch. Neuron, 69(5), 918 - 929. 10.1016/j.neuron.2011.01.030.
  13. Causeret F,Ensini M,Teissier A,Kessaris N,Richardson WD,Lucas de Couville T,Pierani A (2011) Dbx1-expressing cells are necessary for the survival of the mammalian anterior neural and craniofacial structures. PLoS One, 6(4), e19367. 10.1371/journal.pone.0019367.
  14. Laranjeira C,Sandgren K,Kessaris N,Richardson W,Potocnik A,Vanden Berghe P,Pachnis V (2011) Glial cells in the mouse enteric nervous system can undergo neurogenesis in response to injury. J Clin Invest, 121(9), 3412 - 3424. 10.1172/JCI58200.
  15. Calvo CF,Fontaine RH,Soueid J,Tammela T,Makinen T,Alfaro-Cervello C,Bonnaud F,Miguez A,Benhaim L,Xu Y,Barallobre MJ,Moutkine I,Lyytikkä J,Tatlisumak T,Pytowski B,Zalc B,Richardson W,Kessaris N,Garcia-Verdugo JM,Alitalo K,Eichmann A,Thomas JL (2011) Vascular endothelial growth factor receptor 3 directly regulates murine neurogenesis. Genes Dev, 25(8), 831 - 844. 10.1101/gad.615311.
  16. Rinholm JE,Hamilton NB,Kessaris N,Richardson WD,Bergersen LH,Attwell D (2011) Regulation of oligodendrocyte development and myelination by glucose and lactate. J Neurosci, 31(2), 538 - 548. 10.1523/JNEUROSCI.3516-10.2011.
  17. Zawadzka M,Rivers LE,Fancy SPJ,Zhao C,Tripathi R,Jamen F,Young K,Goncharevich A,Pohl H,Rizzi M,Rowitch DH,Kessaris N,Suter U,Richardson WD,Franklin RJM (2010) CNS-Resident Glial Progenitor/Stem Cells Produce Schwann Cells as well as Oligodendrocytes during Repair of CNS Demyelination CELL STEM CELL, 6(6), 578 - 590. 10.1016/j.stem.2010.04.002.
  18. Tripathi RB,Rivers LE,Young KM,Jamen F,Richardson WD (2010) NG2 glia generate new oligodendrocytes but few astrocytes in a murine experimental autoimmune encephalomyelitis model of demyelinating disease. J Neurosci, 30(48), 16383 - 16390. 10.1523/JNEUROSCI.3411-10.2010.
  19. Panayi H,Panayiotou E,Orford M,Genethliou N,Mean R,Lapathitis G,Li S,Xiang M,Kessaris N,Richardson WD,Malas S (2010) Sox1 is required for the specification of a novel p2-derived interneuron subtype in the mouse ventral spinal cord Journal of Neuroscience, 30(37), 12274 - 12280.
  20. Panayi H,Panayiotou E,Orford M,Genethliou N,Mean R,Lapathitis G,Li S,Xiang M,Kessaris N,Richardson WD,Malas S (2010) Sox1 is required for the specification of a novel p2-derived interneuron subtype in the mouse ventral spinal cord Journal of Neuroscience, 30(37), 12274 - 12280.
  21. Young KM,Mitsumori T,Pringle N,Grist M,Kessaris N,Richardson WD (2010) An Fgfr3-iCreER(T2) transgenic mouse line for studies of neural stem cells and astrocytes. Glia, 58(8), 943 - 953. 10.1002/glia.20976.
  22. Psachoulia K,Jamen F,Young KM,Richardson WD (2009) Cell cycle dynamics of NG2 cells in the postnatal and ageing brain. Neuron Glia Biol, 5(3-4), 57 - 67. 10.1017/S1740925X09990354.
  23. Li H,He Y,Richardson WD,Casacchia P (2009) Two-tier transcriptional control of oligodendrocyte differentiation. Current Opinion in Neurobiology, Epub in advance. 10.1016/j.conb.2009.08.004.
  24. Gomez-Sanchez JA,Lopez de Armentia M,Lujan R,Kessaris N,Richardson WD,Cabedo H (2009) Sustained axon-glial signalling induces Schwann cell hyperproliferation, Remak bundle myelination and tumorigenesis. Journal of Neuroscience, 29(36), 11304 - 11315. 10.1523/JNEUROSCI.1753-09.2009.
  25. Genethliou N,Panayiotou E,Panayi H,Orford M,Mean R,Lapathitis G,Gill H,Raoof S,Gasperi RD,Elder G,Kessaris N,Richardson WD,Malas S (2009) Sox1 links the function of neural patterning and Notch signalling in the ventral spinal cord during the neuron-glial fate switch Biochemical and Biophysical Research Communications.
  26. Li H,Richardson WD (2009) Genetics meets epigenetics: HDACs and Wnt signalling in oligodendrocyte development and regeneration. Nature Neuroscience, 12(7), 815 - 817. 10.1038/nn0709-815.
  27. Anselmi F,Hernandez H,Crispino G,Seydel A,Ortolano S,Roper SD,Kessaris N,Richardson WD,Rickheit G,Filippov M,Monyer H,Mammano F (2008) ATP release through connexin hemichannels and gap junction transfer of second messengers propagate Ca2+ signals across the inner ear Proceedings of the National Academy of Sciences of the United States of America, 105(48), 18770 - 18775. 10.1073/pnas.0800793105.
  28. Pontecorvi M,Goding CR,Richardson WD,Kessaris N (2008) Expression of Tbx2 and Tbx3 in the developing hypothalamic-pituitary axis Gene Expression Patterns, 8(6), 411 - 417. 10.1016/j.gep.2008.04.006.
  29. Zhou L,Bar I,Achouri Y,Campbell K,De Backer O,Hebert JM,Jones K,Kessaris N,Lambert de Rouvroit C,O'Leary D,Richardson WD,Goffinet AM,Tissir F (2008) Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice Science, 320(5878), 946 - 949. 10.1126/science.1155244.
  30. Müller SM,Stolt CC,Terszowski G,Blum C,Amagai T,Kessaris N,Iannarelli P,Richardson WD,Wegner M,Rodewald H-R (2008) Neural crest origin of perivascular mesenchyme in the adult thymus The Journal of Immunology, 180(8), 5344 - 5351.
  31. Li HL,Richardson WD (2008) The evolution of Olig genes and their roles in myelination NEURON GLIA BIOL, 4, 129 - 135. 10.1017/S1740925X0999025.
  32. Kessaris N,Pringle N,Richardson WD (2008) Specification of CNS glia from neural stem cells in the embryonic neuroepithelium Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences, 363(1489), 71 - 85. 10.1098/rstb.2006.2013.
  33. Richardson WD (2008) Oligodendrocyte specification.
  34. Rivers LE,Young KM,Rizzi M,Jamen F,Psachoulia K,Wade A,Kessaris N,Richardson WD (2008) PDGFRA/NG2 glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice. Nature Neuroscience, 11, 1392 - 1401. 10.1038/nn.2220.
  35. Li HL,Lu Y,Smith HK,Richardson WD (2007) Olig1 and Sox10 interact synergistically to drive Myelin Basic Protein transcription in oligodendrocytes J NEUROSCI, 27(52), 14375 - 14382. 10.1523/JNEUROSCI.4456-07.2007.
  36. Billon N,Iannarelli P,Monteiro MC,Glavieux-Pardanaud C,Richardson WD,Kessaris N,Dani C,Dupin E (2007) The generation of adipocytes by the neural crest. Development, 134, 2283 - 2292.
  37. Del Barrio MG,Taveira-Marques R,Muroyama Y,Yuk D-I,Li S,Wines-Samuelson M,Shen J,Smith HK,Xiang M,Rowitch D,Richardson WD (2007) A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool Development, 134(19), 3427 - 3436.
  38. Del Barrio MG,Taveira-Marques R,Muruyama Y,Yuk DI,Li S,Wines-Samuelson M,Shen J,Smith HK,Xiang M,Rowitch D,Richardson WD (2007) A gene network involving Foxn4, Mash1 and Delta-like 4/Notch-1 specifies V2a and V2b spinal interneurons from a common progenitor pool Development, 134, 3427 - 3436. 10.1242/dev.005868.
  39. Costa MR,Kessaris N,Richardson WD,Götz M,Hedin-Pereira C (2007) The marginal zone/layer I as a novel niche for neurogenesis and gliogenesis in developing cerebral cortex Journal of Neuroscience, 27(42), 11376 - 11388. 10.1523/JNEUROSCI.2418-07.2007.
  40. Young K,Fogarty M,Kessaris N,Richardson WD (2007) Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb Journal of Neuroscience, 27, 8286 - 8296. 10.1523/JNEUROSCI.0476-07.2007.
  41. Kessaris N,Fogarty M,Iannarelli P,Grist M,Wegner M,Richardson WD (2006) Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. Nature Neuroscience, 9, 173 - 179. 10.1038/nn1620.
  42. Richardson WD,Kessaris N,Pringle NP (2006) Oligodendrocyte Wars. Nature Reviews Neuroscience, 7, 11 - 18.
  43. Kazakova N,Li H,Mora A,Jessen K,Mirsky R,Richardson WD,Smith HK (2006) A screen for mutations in zebrafish that affect myelin gene expression in Schwann cells and oligodendrocytes Developmental Biology, 297, 1 - 13. 10.1016/j.ydbio.2006.03.020.
  44. Stolt CC,Schlierf A,Lommes P,Hillgärtner S,Werner T,Kosian T,Sock E,Kessaris N,Richardson WD,Lefebvre VW,M (2006) SoxD proteins influence multiple stages of oligodendrocyte development and modulate SoxE protein function. Developmental Cell, 11, 697 - 709.
  45. West H,Richardson WD,Fruttiger MA (2005) Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes. Development, 132, 1855 - 1862. 10.1242/dev.01732.
  46. Matsuoka T,Ahlberg PE,Kessaris N,Iannarelli P,Dennehy U,Richardson WD,McMahon AP,Koentges G (2005) Neural crest origins of the neck and shoulder. Nature, 436, 347 - 355.
  47. Fogarty M,Richardson WD,Tekki-Kessaris N (2005) A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord. Development, 132, 1951 - 1959. 10.1242/dev.01777.
  48. Kessaris N,Jamen F,Rubin LL,Richardson WD (2004) Cooperation between Sonic hedgehog and fibroblast growth factor/MAPK signalling pathways in neocortical precursors Development, 131, 1289 - 1298. 10.1242/dev.01027.
  49. Perry P,Sauer S,Billon N,Richardson WD,Spivakov M,Warnes G,Livesey FJ,Merkenschlager M,Fisher AG,Azuara V (2004) A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction CELL CYCLE, 3(12), 1645 - 1650.
  50. Woodruff RF,Fruttiger M,Richardson WD,Franklin RJM (2004) Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult CNS and their response following CNS demyelination Molecular and Cellular Neuroscience, 25, 252 - 262.

Qualifications

  • 1977: Doctor of Philosophy, King's College London
  • 1973: Bachelor of Science (Honours), University of Manchester

Keywords

  • BAC recombination and related transgene approaches
  • Behaviour
  • Cell culture
  • Confocal microscopy
  • Demyelination
  • Development
  • Fluorescence microscopy techniques
  • Gene expression
  • Gene expression profiling - tissue level
  • Genetic manipulation (including knockout/knockin)
  • Gliomas
  • Histology
  • In vivo electroporation, ionophoresis and microinj
  • Interneurons
  • Ischaemic stroke
  • MiRNA analysis
  • Microarrays
  • Motor Neurone Disease
  • Mouse
  • Multiple Sclerosis
  • Myelin
  • Neocortex
  • Neural Circuits/Networks
  • Neural stem cells
  • Neural stem cells and their progeny.
  • Neurogenesis
  • Oligodendrocytes
  • Progenitors
  • Protein transport/localisation
  • Remyelination
  • Spinal cord
  • Spinal cord injury
  • Stem cells
  • Time-lapse imaging
  • Transgenic mice
  • Zebrafish