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Temporal reconstruction of tRNA abundance during cortical development in progeni...
The cerebral cortex with its range of specialized excitatory projection neurons is essential to the high-order cognitive functions of the brain. These hundreds of subtypes of projection neurons arise from a uniform pool of multipo... The cerebral cortex with its range of specialized excitatory projection neurons is essential to the high-order cognitive functions of the brain. These hundreds of subtypes of projection neurons arise from a uniform pool of multipotent apical progenitors (APs) which sequentially generate neuronal progeny with distinct fates over time. Recent technological advances in single cell transcriptomics revealed the existence transcriptional programs that seed neuronal diversity. While this working model provides a good explanation for the developmental origin of the distinct neuronal subtypes, it is flawed by the existence of some non-correlating mRNAs and proteins. Indeed, a significant fraction of mRNA that characterizes mature neurons can already be found untranslated in progenitors. The additional mechanisms that coordinate the protein synthesis and ensure correct protein expression in progenitors and daughter neurons have not been identified yet. This project focuses on solving the timely question of which mechanisms, synergically with transcription, are required to refine gene expression during neurodevelopment and cortical patterning. To do so, we explore the role of translation and its critical adaptor molecule, the transfer RNA (tRNA), in regulating the competency of APs to generate distinct neuronal fate during mouse embryonic cortices development. We will generate a comprehensive view of tRNAs abundance and translation efficiency in APs at ages E12 to E17. This will uncover a novel regulatory role for tRNAs, updating the conventional view of them as housekeeping genes, and find new candidate genes for cortical development in both health and disease. All in all, we will provide a new working model for how neuronal fate and diversity are regulated and opens avenues for future research in other developmental fields where translation has been previously overlooked. ver más
31/01/2027
CERBM-GIE
196K€
Perfil tecnológico estimado
Duración del proyecto: 33 meses Fecha Inicio: 2024-04-22
Fecha Fin: 2027-01-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-04-22
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2023-PF-01-01: MSCA Postdoctoral Fellowships 2023
Cerrada hace 1 año
Presupuesto El presupuesto total del proyecto asciende a 196K€
Líder del proyecto
CENTRE EUROPEEN DE RECHERCHE EN BIOLOGIE ET M... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5