Wolfson Institute for Biomedical Research
WIBR Seminar
“Human cerebral cortex development
and disease in stem cell systems”
Dr Rick Livesey
Gurdon Institute
University of Cambridge
Thursday 7th May 2015
The cerebral cortex, which makes up three quarters of the human 4pm
brain, is the part of the nervous system that integrates sensations, The Wolfson Institute for Biomedical Research
executes decisions and is responsible for cognition and perception. st
Given its functional importance, it is not surprising that diseases of 1 Floor Cruciform Building, Cruciform Café
the cerebral cortex are major causes of morbidity and mortality. Gower Street
Understanding the biology of cortical neural stem cells is essential London, WC1E 6BT
for understanding human evolution, the pathogenesis of human alison.kelly@ucl.ac.uk / 020 7679 6134
neurodevelopmental disorders and the rational design of neural
repair strategies in adults. During embryonic development, all of the
neurons in the cortex are generated from a complex population of
multipotent stem and progenitor cells. Much of the research in the
lab centres on the cell and molecular biology of cortical stem cells.
We are particularly interested in the molecular mechanisms
controlling multipotency, self-renewal and neurogenesis, and how
these are coordinated to generate complex lineages in a fixed
temporal order. A number of ongoing projects in the group address
the functional importance of transcriptional and epigenetic
mechanisms in this system.
In the other major strand of research in the group, we have
developed methods for directing differentiation of human
pluripotent stem cells to cortical neurons, via a cortical stem cell
stage. Human stem cell-derived cortical neurons form functional
networks of excitatory synapses in culture. We are using this system
for studies of human neural stem cell biology and to generate
models of cortical diseases. Our initial focus has been on dementia,
where we have used stem cells from people with Down syndrome
and from patients with familial Alzheimer’s disease to create cell
culture models of Alzheimer’s disease pathogenesis in cortical
neurons. We are using those models to study Alzheimer’s disease
pathogenesis and the efficacy of current therapeutic strategies.
www.ucl.ac.uk