Objectif The generation of neurons during development from a fertilised egg requires a cascade of neuronal lineage-specific genes. This genetic cascade, and in particular the expression of proneural genes, is also required for efficient in vitro reprogramming of adult cells into neuronal cells for replacement therapies. Yet the upstream molecular events that directly regulate the expression of proneural transcription factors during embryogenesis remain ambiguous. The specification of neuronal lineages is further complicated by the fact that it needs to be coordinated across the left-right (L/R) axis. Our nervous system, like our body, is largely bilaterally symmetric yet both molecular and anatomical L/R asymmetries are also observed in the brain. Disruptions of bilateral and L/R asymmetric organisation in the human brain are frequently observed in Parkinson’s disease, schizophrenia and epilepsy. How symmetric and asymmetric neural determination programs are coordinated to establish a fully functional nervous system is poorly understood.The first key aim of this proposal is to identify the cis-regulatory mechanisms and trans-acting factors that control both symmetric and asymmetric proneural gene expression in C. elegans using a combination of in vivo promoter analysis and reverse genetics. The second key aim of this proposal is to identify and characterise through forward genetic screens, 4D-lineage analysis and second-generation sequencing approaches, novel factors that act in two specific neuronal lineages to either (a) impart bilaterally symmetric neurogenesis or (b) regulate asymmetric neurogenesis. Since many principles of neural development are conserved from nematodes to vertebrates, defining in more detail the early steps of bilaterally symmetric and asymmetric neurogenesis in vivo in this genetic model system will allow us to generate neurons in vitro more efficiently and will advance our understanding and prevention of human neurological disease. Champ scientifique natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicineneurologyepilepsynatural sciencesbiological sciencesdevelopmental biologymedical and health sciencesbasic medicineneurologyparkinsonmedical and health sciencesclinical medicinepsychiatryschizophrenia Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Thème(s) FP7-PEOPLE-2013-CIG - Marie-Curie Action: "Career Integration Grants" Appel à propositions FP7-PEOPLE-2013-CIG Voir d’autres projets de cet appel Régime de financement MC-CIG - Support for training and career development of researcher (CIG) Coordinateur UNIVERSITY COLLEGE LONDON Contribution de l’UE € 100 000,00 Adresse GOWER STREET WC1E 6BT London Royaume-Uni Voir sur la carte Région London Inner London — West Camden and City of London Type d’activité Higher or Secondary Education Establishments Contact administratif Giles Machell (Mr.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
