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Richardson Lab at UCL    Neural development and plasticity

William D Richardson PhD FMedSci FRS

Wolfson Institute for Biomedical Research

University College London, Gower Street, London WC1E 6BT, UK.

tel +44 (0)20 7679 6729

assistant:  Alison Kelly    lab manager:  Matthew Grist

Cell-cell interactions in the developing central nervous system  The vertebrate central nervous system (CNS) is immensely complicated, yet it has simple beginnings. The huge number and variety of cells in the mature CNS all develop from a much smaller number of precursor (stem) cells in the embryonic neural tube. Two of the central questions of neurodevelopment - and development in general - are: 1) How do stem cells select their future fates? 2) How do stem cells generate their differentiated progeny in correct numerical proportion to each other and to the size of the embryo as a whole? We are addressing these issues, focusing on the development of glial progenitor cells in the CNS. We take a multidisciplinary approach including primary cell culture, in situ methods and genetic manipulation in mice (e.g. Li et al., 2011, Tsai et al., 2012)

Neural plasticity  Pools of precursor/ stem cells persist in the adult CNS.  Some inhabit the subventricular zones (SVZ) of the forebrain where they produce new neurons for the olfactory bulb throughout life.  Others reside in the hippocampus and continuously generate new hippocampal interneurons in the adult.  Another population of neural precursor cells - adult oligodendrocyte progenitors (OLPs, also known as NG2 cells) - is scattered uniformly throughout the adult brain and spinal cord.  We showed recently (Rivers et al., 2008; Young et al., 2013) that NG2 cells continue to generate new myelinating oligodendrocytes throughout adulthood in mice.  We are now studying the functional role of the late-born oligodendrocytes and the myelin they produce.  One important function is repair of demyelinating damage following CNS injury or disease (Tripathi et al., 2010; Zawadzka et al., 2010).  We have recently shown (McKenzie, Ohayon et al., 2014) that new central myelin is required for mice to learn new motor skills.

William D Richardson  short CV

Kougioumtzidou, E., Shimizu, T., Hamilton, N.B., Tohyama, K., Sprengel, R., Monyer, H., Attwell, D. and Richardson, W.D. (2017).  Signalling through AMPA-type glutamate receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival.  eLife  2017;6:e28080  doi: 10.7554/eLife.28080  joint senior authors

Xiao, L., Ohayon, D, McKenzie, I.A., Sinclair-Wilson, A., Wright, J.L., Fudge, A.D., Emery, B., Li, H. and Richardson, W.D. (2016).  Rapid production of new oligodendrocytes is required in the earliest stages of motor-skill learning.
  Nat Neurosci 19, 1210-1217.

*McKenzie, I.A., *Ohayon, D., Li, H., Paes de Faria, J., Emery, B., Tohyama, K. and Richardson, W.D. (2014).  Motor skills learning requires active central myelination.  Science 346, 318-322.  doi:10.1126/science.1254960   * equal contributions

Young, K.M., Psachoulia, K., Tripathi, R.B., Dunn, S.-J., Cossell, L., Attwell, D., Tohyama, K. and Richardson, W.D. (2013). Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodelling.  Neuron 77, 873-885.

Tsai, H.-H., Li, H., Fuentealba, L., Molofsky, A.V., Taveira‑Marques, R., Zhuang, H., Tenney, A., Murnen, A.T., Fancy, S.P.J., Merkle, F., Kessaris, N., Alvarez‑Buylla, A.*, Richardson, W.D.* and Rowitch, D.H.* (2012).  Regional astrocyte allocation regulates CNS synaptogenesis and repair.  Science 337, 358-362.  *joint senior authors

Li, H., Paes de Faria, J., Andrew, P. Nitarska, J. and Richardson, W.D. (2011).  Phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch.  Neuron 69, 918-929.

Tripathi, R.B., Rivers, L.E., Jamen, F. Young, K.M. and Richardson, W.D. (2010). NG2 glia generate new oligodendrocytes but few astrocytes in a murine experimental autoimmune encephalomyelitis model of demyelinating disease.  J. Neurosci. 30, 16383-16390.

Zawadzka, M., Rivers, L., Fancy, S.P.J., Zhao, C., Tripathi, R., Jamen, F., Young, K.M.,Goncharevich, A., Pohl, H., Rizzi, M., Rowitch, D.H., Kessaris, N., Suter, U., *Richardson, W.D. and *Franklin, R.J.M. (2010). CNS-resident glial progenitor/stem cells produce Schwann cells as well as oligodendrocytes during repair of CNS demyelination. Cell Stem Cell 6, 578-590.   * joint senior authors

Rivers, L.E., Young, K.M., Rizzi, M., Jamen, F., Psachoulia, K., Wade, A., Kessaris, N. and Richardson, W.D. (2008).  PDGFRA/ NG2-positive glia generate myelinating oligodendrocytes and piriform projection neurons in adult mice.  Nature Neuroscience 11, 1392-1401.