Objectif Inhibitory interneurons function as modulators of local circuit excitability. Their properties are of fundamental importance for normal brain function therefore understanding how these cells are generated during development may provide insight into neurodevelopmental disorders such as epilepsy and schizophrenia, in which interneuron defects have been implicated. Inhibitory GABAergic interneurons of the cerebral cortex (pallium) are generated from proliferating subpallial precursors during development and migrate extensively to populate the cortex. The aim of this proposal is to identify genetic pathways and signalling systems that underlie cortical interneuron migration and integration into functional neuronal circuits. Distinct interneuron subtypes are generated from the two most prominent neuroepithelial stem cell pools in the subpallium: the medial ganglionic eminence (MGE) and the lateral/caudal ganglionic eminence (LGE/CGE). We will genetically tag and purify interneurons originating from these precursors in order to examine their transcriptomes and identify factors involved in specification and migration. We will use Cre-lox fate mapping in transgenic mice to label specific sub-populations of neural stem cells and their differentiated progeny in the embryonic telencephalon. This will allow us to determine whether subdomains of the MGE or LGE/CGE neuroepithelium generate interneurons with distinct neurochemical phenotypes and/or characteristic migratory properties. Electrical activity and/or neurotransmitter receptor activation can act in concert with genetic programs to promote precursor proliferation, neuronal differentiation as well as neuronal migration. We will use gain-of-function and loss-of-function approaches to examine the role of neurotransmitters and neuropeptides at early stages of interneuron migration to the cortex. Champ scientifique natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologyepilepsymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicinepsychiatryschizophrenia Mots‑clés cell migraton cortex fate-mapping interneurons mouse molecular genetics Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) ERC-SG-LS1 - ERC Starting Grant - Molecular and Structural Biology and Biochemistry Appel à propositions ERC-2007-StG Voir d’autres projets de cet appel Régime de financement ERC-SG - ERC Starting Grant Institution d’accueil UNIVERSITY COLLEGE LONDON Contribution de l’UE € 1 250 000,00 Adresse GOWER STREET WC1E 6BT LONDON Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Nicoletta Kessaris (Name On Phd Certificate: Tekki) (Dr.) Contact administratif Michael Browne (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire UNIVERSITY COLLEGE LONDON Contribution de l’UE € 1 250 000,00 Adresse GOWER STREET WC1E 6BT LONDON Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Nicoletta Kessaris (Name On Phd Certificate: Tekki) (Dr.) Contact administratif Michael Browne (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
