4 YEAR PhD IN NEUROSCIENCE
The Wolfson Institute for Biomedical Research, UCL
Neuroglial stem/progenitor cells
We study the development and functions of glial cells (oligodendrocytes and astrocytes) during embryogenesis and adulthood. Oligodendrocytes, the myelin-forming cells of the CNS, insulate axons and are required for rapid conduction of action potentials. In the spinal cord, most oligodendrocytes develop from ventral precursor/stem cells (the same precursors as motor neurons) but a smaller subset develops from dorsally-located precursors. An analogous situation pertains in the brain. We are investigating the signalling pathways that specify ventral versus dorsal oligodendrocyte lineages, and whether the different lineages have distinct properties.
Oligodendrocytes continue to be generated during adulthood from “adult oligodendrocyte precursors” or “NG2 cells” that persist in the adult brain and spinal cord. The adult-born oligodendrocytes generate new myelin in the corpus callosum and other fibre tracts; this would be expected to alter the properties of the late-myelinating axons and their neural circuits, suggesting that myelin might play a more active role in neural plasticity (e.g. motor skills learning) than previously recognized.
We showed recently that there are different classes of neural stem cell in the adult subventricular zone (SVZ). These have different embryonic origins, occupy different territories in the SVZ and generate different subsets of olfactory interneurons during adulthood. We are continuing to study the biology and developmental origins of these SVZ stem cells.
Possible rotation projects:
1) Postnatal NG2 cells. By cumulative BrdU uptake assays we showed that there are two classes of NG2 cell in adult white matter; around half divide with a period of around one week and the other half never divide (i.e. they are post-mitotic). Other labs have described two classes of NG2 cells based on different criteria - for example, spiking and non-spiking subtypes. We ourselves showed that NG2 cells in the adult corpus callosum have different embryonic origins, being derived from either the ventral (striatal) or dorsal (cortical) germinal zones. The student will investigate the relationship between the mitotic status of NG2 cells and 1) their embryonic origin, 2) their electrophysiological properties (in collaboration with the Attwell lab). These experiments will provide insights into the roles of NG2 cell in the postnatal CNS. Skills learned: tissue preparation, cryosectioning, immunocytochemistry, confocal immunofluorescence microscopy, electrophysiology (in Attwell lab).
2) SVZ stem cells. The student will study the cellular architecture of the forebrain SVZ by immunohistochemistry on flat-mount tissue preparations and sections. He/she will investigate the stem cell niche in vivo, mapping the spatial distribution of stem cells and their relationships with ependymal cells and other cells (e.g. vasculature) in the adult SVZ. Skills learned: tissue preparation, cryosectioning, microdissection, immunocytochemistry, confocal immunofluorescence microscopy, gross and cellular neuroanatomy. The student will also learn about neural stem cell biology and adult neurogenesis.
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 cortical projection neurons in adult mice.
Nat. Neurosci. published online: 8 October 2008 | doi:10.1038/nn.2220
Young, K., Fogarty, M., Kessaris, N. and Richardson, W.D. (2007)
Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb.
J. Neurosci. 27, 8286-8296
Kessaris, N., Fogarty, M., Iannarelli, P., Grist, M., Wegner, M. and Richardson, W.D (2006)
Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage. (see News and Views: Ventura, R.E. and Goldman, J.E. (2006). Nat. Neurosci. 9,153-154)
Nat. Neurosci. 9, 173-179.
Richardson, W.D., Kessaris, N. and Pringle, N.P. (2006)
Nat. Rev. Neurosci. 7, 11-18