Research in the Kessaris Lab
study neuronal development from embryonic neural stem cells
focusing on neuronal subtypes generated from subpallial precursors in
the embryo. We
examine the genetic basis of neuronal subtype specification, migration,
differentiation and circuit integration. We use genetic manipulation in
mice to fate-map precursor cells, tag and purify stem cells and their
progeny in order to identify genes involved in their development. We
manipulate gene function using loss- and gain-of-function approaches and assess the physiological and behavioural consequences. Our work is aimed at understanding normal development and the contribution of abnormalities to neurodevelopmental disorders.
Cortical Interneuron Development and Contribution to Neurodevelopmental Disorders
in the adult cortex represent a heterogeneous population of cells in
terms of morphology, neurochemical and physiological properties. It is
unknown how this diversity arises, what the significance of the
diversity is and what the function of these interneuron subtypes might
be in cortical circuits. Using
genetic fate-mapping approaches we labelled molecularly distinct precursor
cells and identified their neuronal progeny. This enabled us to map the embryonic origins of cortical interneurons and provided us
with tools to further manipulate their function. We demonstrated that interneuron diversity is
specified to a large extent during embryogenesis and, unlike projection
neurons of the cortex which are generated from resident cortical
precursors, interneurons are generated from distant neuroepithelial
stem cells in the ventral telencephalon and migrate long distances to
reach the cortex. We are assessing the molecular basis of interneuron
number regulation and subtype specification using genetic tools. As cortical interneurons have been implicated in seizure-based and neurodevelopmental disorders such as autism spectrum disorders we are examining the contribution of interneuron dysfunction to such disorders using a range of behavioural assays.
Septal Neurogenesis, Diversity and Function
septal complex forms an integral part of the limbic system connecting the telencephalon with the hypothalamus and brain stem. Through reciprocal connections with the hippocampus and rhythmic drive of hippocampal network oscillations, the septum has a prominent role in cognitive processing. Despite its fundamental role, the septum has received relatively little attention.
We use genetic tools to dissect the embryonic origin of septal neurons. Using genetic deletions and electrophysiology in behaving animals in collaboration with prominent groups at UCL we relate specific neural cell populations at a mechanistic level to particular brain functions.
Last updated January 2016