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Role of cell lineage in the generation of neuronal diversity in the mouse cerebral cortex

Descripción del proyecto

Los orígenes del desarrollo de la diversidad neuronal.

La ejecución de funciones cerebrales de orden superior, como la cognición y el control motor sofisticado, requiere una amplia diversidad de neuronas. Durante el desarrollo, los procesos de especificación del destino celular determinan la generación de diferentes tipos neuronales a partir de células progenitoras. Comprender los principios que sustentan la generación de la identidad neuronal requiere seguir la progresión del linaje celular de células progenitoras a neuronas con resolución unicelular. Para facilitar esto, el proyecto NEURORIGINS financiado con fondos europeos desarrollará herramientas para atacar genéticamente subconjuntos específicos de progenitores neuronales en la corteza cerebral del ratón. El etiquetado de estos progenitores permitirá su rastreo durante el desarrollo y proporcionará información sobre cómo producen una progenie neural diferente. El proyecto generará información importante sobre las vías de desarrollo que conducen a la diversidad neuronal.

Objetivo

Cell lineage is an important determinant in the generation of neuronal diversity. Understanding the relation between cell lineage and neuronal identity is critical to know where and when cell fate decisions take place during development. In Drosophila, different neuronal types emerge from specific parts in the lineage tree. Some neuronal types specifically arise from certain branches (fate-restricted progenitor cells). Other neuronal types emerge from the same branch but at different times, following a temporal sequence. Whereas neuronal specification in mice seems to follow slightly different rules, the lack of appropriate tools to consistently target the same progenitor cells and following lineage progression with single-cell resolution has limited our understanding of this process. I thereby hypothesize that, similar to Drosophila, different neuronal types systematically emerge from dedicated parts of the lineage tree, although methodological limitations have impeded to prove this hypothesis. NEURORIGINS aims to fill this gap by producing tools to genetically target specific subsets of neuronal progenitors in the mouse cerebral cortex (Objective 1). To find fate-restricted neuronal progenitors and link these progenitors with specific types of projection neurons, I will use these tools to label and identify the neuronal progeny derived from these progenitor cells (Objective 2). In the last phase, I will follow the temporal progression of these sublineages, exploring whether some types of projection neurons are generated from the same sublineage over different developmental windows (Objective 3). Besides unveiling important insights on the developmental pathways resulting on neuronal diversity in the mouse brain, NEURORIGINS will provide me with a new set of technical and transferable skills that will be critical for my future as an independent researcher.

Coordinador

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Aportación neta de la UEn
€ 160 932,48
Dirección
CALLE SERRANO 117
28006 Madrid
España

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Región
Comunidad de Madrid Comunidad de Madrid Madrid
Tipo de actividad
Research Organisations
Enlaces
Coste total
€ 160 932,48