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)
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
(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.
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
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
*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
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.
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,
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.