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4 YEAR PhD IN NEUROSCIENCE

Nicoletta Kessaris

The Wolfson Institute for Biomedical Research, UCL

The Wolfson Institute for Biomedical Research, UCL

Interneurons of the cerebral cortex: development and contribution to neurodevelopmental disorders

Cortical interneurons provide the inhibitory component to cortical circuits. They represent a minority of neurons in the cortex but exhibit a remarkable diversity that is largely set up by genetic specification programs during embryogenesis. Our lab focusses on understanding these programs in model organisms using genetic manipulation. Abnormal development of cortical interneurons contributes to neurodevelopmental disorders such as autism spectrum disorders (ASD). Using loss- and gain-of-function approaches together with behavioural analysis in vivo we aim to explore the contribution of genetic defects to ASD-like behaviour.

Available rotation projects

1) Dissecting genetic pathways that regulate cortical interneuron development and maturation

The student will be involved in analysis of genetic screens aimed at identifying key regulators of cortical interneuron development. Techniques used in this project will include tissue collection and processing, immunohistochemistry and in situ hybridization for expression analysis. This can lead to a longer PhD project where loss- and gain-of-function approaches together with complementation analysis are used to identify developmentally relevant cortical interneuron specification pathways.

2) Assessing the role of cortical interneuron development on cortical maturation and ASD-like behaviour

The student will be involved in the generation of novel transgenic models with disrupted cortical interneuron development. Techniques used in this project will include molecular cloning for vector building and BAC manipulation. This can lead to a longer PhD project where the transgenic mouse is generated and analysed in terms of expression, function and ultimately ASD-like behaviour.

Publications

Kessaris N, Magno L, Rubin AN, Oliveira MG. (2014) Genetic programs controlling cortical interneuron fate. Current Opinion in Neurobiology 26C:79-87.

Rubin AN, Kessaris N. (2013) PROX1: a lineage tracer for cortical interneurons originating in the lateral/caudal ganglionic eminence and preoptic area. PLOS One 8(10): e77339.

Magno L, Oliveira MG, Mucha M, Rubin AN, Kessaris N. (2012) Multiple embryonic origins of nitric oxide synthase-expressing GABAergic neurons of the neocortex. Frontiers in Neuroscience 6:65.

Rubin AN, Alfonsi F, Humphreys MP, Choi CKP, Rocha SF and Kessaris N. (2010) The germinal zones of the basal ganglia but not the septum generate inhibitory interneurons for the cortex. Journal of Neuroscience 30(36): 12050-12062.

Gelman DM, Martini FJ, Nóbrega-Pereira S, Pierani A, Kessaris N, Marín O. (2009) The embryonic preoptic area is a novel source of cortical GABAergic interneurons. Journal of Neuroscience 29(29): 9380-9.

Nóbrega-Pereira S, Kessaris N, Du T, Kimura S, Anderson SA, Marín O. (2008) Postmitotic Nkx2-1 controls the migration of telencephalic interneurons by direct repression of guidance receptors. Neuron 59(5): 733-45.

Fogarty M, Grist M, Gelman D, Marín O, Pachnis V, Kessaris N. (2007) Spatial genetic patterning of the embryonic neuroepithelium generates GABAergic interneuron diversity in the adult cortex. Journal of Neuroscience 27(41): 10935-46.