Projet de thèse en Neurosciences - Neurobiologie
Sous la direction de Sandrine Humbert.
Thèses en préparation à Grenoble Alpes , dans le cadre de École doctorale chimie et science du vivant (Grenoble) , en partenariat avec GIN - Grenoble Institut des Neurosciences (laboratoire) depuis le 01-10-2014 .
Pas de résumé en français disponible.
Huntingtin in adult neurogenesis
Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disorder characterized by psychiatric disorders, cognitive decline and disturbance of muscle coordination. HD is caused by the mutation of the huntingtin protein (HTT). Both gain of new toxic functions of mutant HTT and loss of the functions of the wild-type HTT contribute to disease progression. HTT is widely expressed in the early developing mouse embryo where it has an essential role. It is crucial for the nervous system development and for embryonic neurogenesis. HTT is also important for adult neurogenesis: it influences the maturation of newly generated neurons in the hippocampus. Adult neurogenesis is known to participate to learning and memory, functions that are affected in HD patients. Several data from our laboratory suggest that HTT is crucial during different steps of adult hippocampal neurogenesis. The aim of my PhD project is to address specifically the contribution of HTT to the maintenance of the pool of neural stem cells and to describe the underlying mechanisms. Notably, I will present evidence that HTT could interact with one of the main signaling pathway of neural stem cells, the Notch pathway. To reach the goal of my project, I combine the use of in vitro and in vivo approaches: adult hippocampal stem cell cultures (from the dentate gyrus (DG) of adult mice), and mouse model in which HTT is depleted from neural stem cells