Description du projet
Comprendre l’architecture clonale du cerveau mature
Le cerveau est un complexe de cellules neuronales et gliales dont l’architecture clonale et le rôle dans les circuits neuronaux ne sont que partiellement explorés. Le projet BRAINSTRUCT, financé par le CER, vise à élucider les aspects de l’architecture clonale du cerveau qui sont essentiels au développement, à la structure et à la fonction des circuits neuronaux, ainsi qu’à l’étiologie des troubles du développement neurologique. La recherche utilisera de nouvelles stratégies transgéniques pour suivre simultanément la lignée de plusieurs cellules souches neurales individuelles dans le cerveau intact de la souris. Cette approche interdisciplinaire permettra de découvrir comment les interactions cellulaires et les signaux intercellulaires régulent la production des cellules souches neurales. Le projet vise à fournir la base d’une analyse quantitative du développement du cerveau à l’aide de technologies à résolution unicellulaire.
Objectif
The brain is an extraordinary complex assembly of neuronal and glial cells that underpins cognitive functions. How adequate numbers of these cells are generated by neural stem cells in embryonic and early postnatal development and how they distribute and interconnect within brain tissue is still debated. In particular, the potentialities of individual neural stem cells, their potential heterogeneity and the mechanisms regulating their function are still poorly characterized in situ; likewise, the clonal architecture of mature brain tissue and its influence on neural circuitry are only partially explored. Deciphering these aspects is essential to link neural circuit development, structure and function, and to understand the aetiology of neurodevelopmental disorders.
We have recently established transgenic strategies to simultaneously track the lineage of multiple individual neural stem cells in the intact developing brain and experimentally perturb their development. We will use these approaches in combination with recent large-volume imaging methods for high-throughput analysis of individual neural and glial clones in the mouse cortex. This will allow us to assay neural progenitor potentialities and equivalence, characterize developmental changes occurring in the neurogenic niche, describe the clonal organization of the mature cortex and study its link with neural connectivity. To decipher intrinsic and extrinsic mechanisms regulating neural progenitor activity and understand how they produce appropriate numbers of cells, we will assay the outcome of functional perturbations targeting key steps of neural development, introduced in precursors or in their local environment. These experiments will reveal how neural stem cell output might be regulated by cell interactions and intercellular signals. This multidisciplinary project will set the basis for quantitative analysis of brain development with single-cell resolution in normal and pathological conditions.
Champ scientifique
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
CORDIS classe les projets avec EuroSciVoc, une taxonomie multilingue des domaines scientifiques, grâce à un processus semi-automatique basé sur des techniques TLN.
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
75006 Paris
France