Project description
Dissecting the emergence of neuronal identity
Neuronal diversity determines an organism's behaviour and emerges from cell intrinsic and extrinsic interactions during development. Dissecting neuronal identity in the brain has been hampered by the extensive heterogeneity and interconnectivity of neurons, which display dynamic sensitivities to various signals. To address this problem, the EU-funded NATURE_NURTURE project will employ the developing neocortex as a model system to identify the molecular determinants of neuronal identity. Using various approaches including genetic manipulation, scientists aim to distinguish the intrinsic and extrinsic drivers of cell identity, hoping to advance circuit repair through the transplantation of engineered neuronal cell types.
Objective
Neuronal diversity determines the variety of circuits that can be formed and thus sets the framework for an animals behavioural repertoire. During development, distinct neuronal types emerge from interactions between cell-intrinsic processes and cell-extrinsic processes. In the brain, untangling how intrinsic and extrinsic processes contribute to neuronal identity has been difficult, as neurons are highly interconnected and heterogeneous cells with distinct and dynamic sensitivities to environmental signals. In such conditions, high temporal single-cell resolution approaches are required to parse out the drivers of cell-type differentiation.
The mouse neocortex is an ideal model to tease out drivers of differentiation: radially, cell-intrinsic genetic mechanisms drive the generation of successive neuron types across cortical layers; tangentially, cell-extrinsic processes are critical to drive differentiation via synaptic input across cortical areas. Here, using the developing neocortex as a model system, I propose to identify how cell-intrinsic and -extrinsic processes interact to define distinct neuron identities by characterizing:
1. emergence of area-specific neuronal and progenitor identities using FlashTag fate mapping and single-cell RNA sequencing (Work Package (WP) 1)
2. plasticity of area-specific neuronal states in response to genetic manipulation, transplantation or input/activity manipulation (WP2)
3. spatial context-independent components of neuron identity, by uncovering core molecular and circuit states in vitro (WP3)
4. postnatal experience-dependent controls over neuronal identity, using the precocial rodent Acomys as a new model to study the role of early brain-world interactions (WP4).
Together, these experiments aim to identify the molecular determinants of progenitor and neuron types by distinguishing intrinsic and extrinsic drivers of cell identity, with the long-term aim of reverse-engineering tailored neuronal cell-types for circuit repair.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences genetics RNA
- medical and health sciences clinical medicine transplantation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-ADG - Advanced Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2019-ADG
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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.
1211 Geneve
Switzerland
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