Description du projet
Détailler la formation des neurones dans le cerveau
Le processus de formation de nouveaux neurones dans le cerveau, la neurogenèse, est censé intervenir tout au long de la vie dans des régions spécifiques. De nombreux aspects de ce processus demeurent cependant mal compris. Financé par le Conseil européen de la recherche, le projet EDeN étudiera le rôle de la niche neurogène et en particulier le soutien apporté par les cellules épendymaires. Ces cellules sont d’origine épithéliale et jouent un rôle crucial dans la circulation du liquide céphalo-rachidien et la migration des nouveaux neurones. Les chercheurs vont étudier les processus cellulaires et moléculaires impliqués dans le développement et la différenciation des cellules épendymaires. Les résultats de leurs recherches pourraient mener à la découverte de nouvelles cibles thérapeutiques pour les troubles neurologiques graves.
Objectif
Understanding how billions of neurons are born, migrate and integrate into functional circuits has proved useful in elucidating the pathomechanisms of many neurodevelopmental disorders. Multiciliated ependymal cells have attracted less interest and their development is still enigmatic. However, their strategic location at the interface between brain ventricles and parenchyma and their unique morphology and functions strongly suggest that defects in the generation of these cells may be associated with a variety of severe neurological disorders.
Multiciliated ependymal cells are epithelial cells that line all brain ventricles. The coordinated and oriented beating of their cilia is crucial for the flow of cerebrospinal fluid through the ventricles and the migration of new neurons. These cells also provide physical and trophic support that creates a permissive neurogenic environment in the adult.
We have shown that elongated bipolar radial glial cells transform into ependymal cells at late embryonic stages through mechanisms that remain largely to be explored. The overall objective of this grant application is to develop a new line of research to understand the cellular and molecular mechanisms involved in ependymal cell development. We will use a multidisciplinary approach involving mouse molecular genetics, biophysical approaches, ex-vivo culture systems and advanced live cell imaging to investigate: i) the mechanisms that direct the transformation of RGC into ependymal cells; ii) the mechanisms of centriole amplification in ependymal cell progenitors; iii) how developing ependymal cells contribute to ventricular morphogenesis and adult neurogenesis. This ambitious project will pave the way for the identification of new therapeutic targets for a variety of neurological disorders.
Champ scientifique
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
75654 Paris
France