Descripción del proyecto
Determinar la diversidad neuronal de la corteza cerebral
La corteza cerebral es la capa externa del encéfalo. Se encarga de la memoria, el pensamiento y el aprendizaje, además de estar formada por diversos tipos de neuronas. La investigación sobre el origen de esta diversidad neuronal ha subrayado el papel en la regulación traslacional. El equipo del proyecto TransNeuroFate, financiado por el Consejo Europeo de Investigación, se centra en cómo la disponibilidad de ARN de transferencia (ARNt) maduro conforma un regulador de la diversidad neuronal. La idea es investigar qué programas de traslación influyen en la determinación del linaje neuronal en la corteza cerebral durante el desarrollo. Los resultados también ayudarán a interpretar los trastornos del neurodesarrollo.
Objetivo
The cerebral cortex is a central structure of the mammalian brain, characterized by a remarkable diversity of neuronal types. Understanding the origin of the extraordinary neuronal diversity is fundamental to understand how cortical architecture and functions emerge during development and remains a critical challenge in cellular and molecular neurobiology.
While the efforts have been focused on transcriptional control, evidence for regulation at the translational level is emerging. I hypothesize that translational control, albeit overlooked, acts in a combinatorial fashion with transcriptional induction to regulate gene expression programs during cortical patterning. I have demonstrated an intimate functional link between cortical development and pools of mature transfer RNA (tRNAs), the major determinant of translation. I, therefore, propose to address how translational control, through the modulation of the availability of mature translationally competent tRNAs, fine-tunes gene expression programs during lineage progression, thereby regulating neuronal diversity. Studying this yet unexplored question should unravel a hitherto unrecognized level of neuronal fate identity determination in the cerebral cortex.
We will combine ribosome profiling, mRNA and tRNA deep sequencing, screening of genetic perturbation and gene manipulation in vivo in the mouse embryonic cortex to i) uncover the specific translational programs that influence neuronal lineages progression; ii) determine how tRNA repertoires (both at the transcriptional and post-transcriptional levels) are shaped to meet the specific translational needs of different cell types during corticogenesis and iii) validate the functional importance of fluctuation in mature tRNA content during cortical development.
This project should bring conceptual advances in the understanding of brain development mechanisms that could be instrumental to interpret the pathological mechanisms of neurodevelopmental disorders.
Ámbito científico
Programa(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régimen de financiación
HORIZON-AG - HORIZON Action Grant Budget-BasedInstitución de acogida
75654 Paris
Francia