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.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesclinical medicinetransplantation
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
1211 Geneve
Switzerland