4 YEAR PhD IN NEUROSCIENCE
The Wolfson Institute for Biomedical Research, UCL
The adult brain consists of a large number of neurons and glial cells all of which are generated during embryogenesis from neuroepithelial stem cells that line the ventricles of the brain. Neuroepithelial cells are highly specialized with respect to the neurons they generate thus creating the extensive neuronal diversity that exists in the adult brain. We are trying to understand the genetic basis underlying neural stem cell specialization during development and the generation of neuronal diversity. We focus mainly on forebrain inhibitory interneurons and their precursors. Forebrain interneurons represent one of the most diverse neuronal subtypes in the CNS and impaired interneuron function in humans has been implicated in neurodevelopmental disorders such as schizophrenia, autism and mental retardation. They are generated from restricted pools of stem cells in the forebrain and migrate extensively to reach their destination. Using state-of-the art molecular genetic tools in model organisms we aim to map out their stem cell origins and determine their migration routes during development. Using loss- and gain-of-function approaches in vivo we are also examining the role of signalling pathways in interneuron specification. Our long term goal is to elucidate genetic programs underlying interneuron specification, diversity and function.
1) Fate-mapping forebrain neural stem cells using transgenic technology in model organisms
2) Examining the role of signalling systems such as Delta-Notch and Sonic hedgehog in forebrain interneuron specification using mutation analysis
3) Use transgenic technology to label and purify specific interneuron subsets for microarray analysis and identification of genetic determinants of interneuron fates
Richardson, W.D., Kessaris, N. and Pringle, P.. (2006)
Nature Reviews Neuroscience Vol 7(1) pp11-18.
Kessaris, N., Fogarty, M., Iannarelli P., Grist, M., Wenger, M. and Richardson, W.D.. (2006)
Competition among oligodendrocyte subpopulations in the forebrain and elimination of an embryonic lineage.
Neuroscience Vol 9(2) pp173-9.
Fogarty, M., Richardson, W.D. and Kessaris, N. (2005)
A subset of oligodendrocytes generated from radial glia in the dorsal spinal cord
Development Vol 132 pp1951-1959
Matsuoka, T., Ahlberg, P., Kessaris, N., Iannarelli, P., Dennehy, U., Richardson, W.D. and Koentges, G.. (2005)
Neural crest origins of the neck and shoulder
Nature Vol 436 pp347-55.