Project description
Regulatory insight into cortical development
The cerebral cortex is the neuronal outer layer of our brain and is responsible for cognitive functions including memory, thinking and learning. Cortical neurons are diverse and arise from multipotent progenitors. Single-cell transcriptomics studies have shown that transcriptional programmes are responsible for this neuronal diversity, but discrepancies between abundance of mRNAs and proteins suggest additional regulatory mechanisms. Funded by the Marie Skłodowska-Curie Actions programme, the TRANSITION project focuses on the role of transfer RNA (tRNA) in refining gene expression during neurodevelopment and cortical patterning. By examining tRNA abundance and translation efficiency during development, the study aims to identify new genes crucial for cortical development, offering a new model for neuronal diversity regulation.
Objective
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.
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. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology cognitive neuroscience
- natural sciences biological sciences genetics RNA
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) HORIZON-MSCA-2023-PF-01
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75654 Paris
France
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