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Building up a brain: understanding how neural stem cell fate and regulation controls nervous tissue architecture

Objective

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.

Host institution

SORBONNE UNIVERSITE
Net EU contribution
€ 1 365 765,50
Address
21 Rue De L'ecole De Medecine
75006 Paris
France
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00

Beneficiaries (2)

SORBONNE UNIVERSITE
France
Net EU contribution
€ 1 365 765,50
Address
21 Rue De L'ecole De Medecine
75006 Paris
Activity type
Higher or Secondary Education Establishments
Non-EU contribution
€ 0,00
Third-party

Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure.

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Net EU contribution
€ 563 947,50
Address
Rue De Tolbiac 101
75654 Paris
Activity type
Research Organisations
Non-EU contribution
€ 0,00