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Area-specific transcriptional dynamics and plasticity of neocortical neurons

Project description

Untangling neuronal plasticity during brain development

Brain development is driven by external signals and cell-intrinsic processes that orchestrate a circuit of diverse neurons. This takes place both before and after birth. Understanding how external signals interact and integrate with internal pathways to produce neuronal identity is necessary for unveiling brain function. The EU-funded ArealPlasticity project will employ a mouse model to study neuronal plasticity using transplantation to mimic the change in the external environment. Researchers aim to identify genes implicated in environmentally triggered neuronal plasticity during differentiation. Results will have important consequences for neurodevelopmental and psychiatric disorders.

Objective

Cellular diversity in the nervous system determines the variety of circuits that set the framework for brain function. These different types of neurons emerge during pre- and post-natal development through the regulation of gene networks by two archetypical processes: cell-intrinsic processes, which are independent of environmental conditions, and cell-extrinsic processes, which are triggered by environmental signals. A continuum of interactions between intrinsic and extrinsic processes underlie cellular states. However, their respective contribution to neuronal identity has been difficult to untangle because neurons are highly interconnected and heterogeneous cell-types with distinct and dynamic sensitivities to environmental signals. Here, using the mouse neocortex as a model system, I will investigate how cell-intrinsic and cell-extrinsic processes interact to define neuronal identities using Patch-seq assessment of neuronal molecular identity following transplantation across cortical areas. Neuronal “plasticity” will be assessed by transplantation, which corresponds to the artificial altering of the environmental factors. Data comparison between transplanted neurons and controls will identify the candidate of “core genes” which regulate the environment-dependent plasticity of neuronal differentiation. Finally, I will manipulate these candidate genes and analyze their effect on final neuronal identity to validate their causal relationship. Altogether, this study will contribute to revealing the plasticity of neuronal identity across cortical areas and to addressing environment-dependent molecular mechanisms controlling the plasticity. In the long term, this may contribute to a better understanding of neurodevelopmental and psychiatric disorders, in which cell-intrinsic and extrinsic factors interact to produce the disease.

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2020

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Coordinator

UNIVERSITE DE GENEVE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 203 149,44
Address
RUE DU GENERAL DUFOUR 24
1211 Geneve
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Genève
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 203 149,44
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