H2020Individual fellowship2020–2022

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

Horizon 2020 — Marie Skłodowska-Curie Actions

Duration
2020-06-01 → 2022-05-31
EU contribution
€160,932
Participants
1
Scheme
MSCA-IF

Lines connect the coordinator with its partners.

Results in brief

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

The nervous system is one of the more diverse in terms of cellular types. In the brain, this diversity includes glial and neuronal types spanning all the functional areas. For instance, hundreds of different neuronal types populate the different layers in the cerebral cortex, which is the brain region that controls the higher cognitive functions such as language or abstract thought. Understanding how different neuronal types originate in this area is probably one of the more interesting questions in neurodevelomental biology. Multiple diseases such as autism or intellectual disability arise as a consequence of errors in the generation of cell diversity in the cerebral cortex. The determinants of neuronal diversity are multiple but mostly unknown. Based on other models in which the generation of neural diversity has been studied in depth, a very heterogeneous pool of neural progenitor cells seems to exist and have a pivotal role on the generation of different neuronal types. However, this remains a matter of debate in the cerebral cortex, where we have not been able to prove this hypothesis. NEURORIGINS aims to identify and characterize different neural progenitors that give rise to diverse neurons, also characterizing how each of these progenitor types produces different neurons at different times.

Data: CORDIS, © European Union

Project 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.

Original text from CORDIS.

Participants

  • AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS · MadridCoordinatorSpain

Links

Data: CORDIS, © European Union