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Richardson Lab at UCL    Neural development, plasticity and repair

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

w.richardson@ucl.ac.uk

assistant:  Andrea Goncalves  andrea.goncalves@ucl.ac.uk    lab manager:  Matthew Grist  m.grist@ucl.ac.uk

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 have addressed these issues, focusing on the development of glial progenitor cells in the CNS. We have taken 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 glia or OPCs) - is scattered uniformly throughout the adult brain and spinal cord.  We showed (Rivers et al., 2008; Young et al., 2013) that NG2 glia continue to divide and 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 also shown that new central myelin is required for mice to learn new motor skills (McKenzie, Ohayon et al., 2014; Xiao et al., 2016) and, more recently, to improve cognitive performance as a result of working memory training (Shimizu, Nayar et al., 2023).  Working memory is a low-capacity, short-term memory system that is important for all sorts of mental tasks such as decision-making or problem-solving; working memory in humans is closely correlated with measures of general or "fluid" intelligence.

William D Richardson  short CV     full CV

*Shimizu, T., *Nayar, S.G., Swire, M., Jiang, Y., Grist, M., Kaller, M., Sampaio Baptista, C., Johansen-Berg, H., Bannerman, D.M., Ogasawara, K., Tohyama,K., Li, H., and Richardson, W.D. (2023). Oligodendrocyte dynamics determine cognitive performance outcomes of working memory training in mice.  Nature Communications 14:6499  * equal first 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.