Project description
The developmental origins of neuronal diversity
The execution of higher-order brain functions such as cognition and sophisticated motor control requires a wide diversity of neurons. During development, cell fate specification processes determine the generation of different neuronal types from progenitor cells. Understanding the principles behind the generation of neuronal identity requires following cell lineage progression from progenitor cells to neurons with single-cell resolution. To facilitate this, the EU-funded NEURORIGINS project will develop tools to genetically target specific subsets of neuronal progenitors in the mouse cerebral cortex. Labelling these progenitors will enable their tracing during development and provide information on how they lead to different neural progeny. The project will provide important insight into the developmental pathways that lead to neuronal diversity.
Objective
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.
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Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
28006 Madrid
Spain