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NATURE_NURTURE

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Intrinsic and extrinsic determinants of neuronal identity

Neuronal diversity determines the variety of circuits that can be formed and thus sets the framework for an animal’s behavioural repertoire. During development, distinct neuronal types emerge from interactions between cell-intrins... ver más

31/08/2025

UNIGE

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

UNIVERSITE DE GENEVE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 2 Participantes

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2020-05-28

ERC-2019-ADG: ERC Advanced Grant

I+D

Cerrada hace 5 años

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2 Participantes

UNIGE

2.50M€ | Lider

SURDRY

153.75K€ | Participante

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Duración del proyecto: 63 meses Fecha Inicio: 2020-05-28
Fecha Fin: 2025-08-31

Líder del proyecto

UNIVERSITE DE GENEVE No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto Neuronal diversity determines the variety of circuits that can be formed and thus sets the framework for an animal’s 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.

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