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Linking time encoded in neural stem cells to neuronal networks through development and evolution

Project description

Neuron-pair study of ‘developmental time’ and circuit formation

The time in a person’s life at which neurons are ‘born’ – developmental time – impacts circuit formation, and thus could also affect aberrant circuit formation as seen in autism spectrum disorder and schizophrenia. With the support of the Marie Skłodowska-Curie Actions programme, the TimeToConnect project aims to shed new light on this phenomenon by conducting the first comprehensive study on how birth date relates to connectivity in an entire neuronal structure. The team will study connections between neurons from different regions of the visual system born at the same time. To do so, they will leverage the recently published complete synaptic-resolution connectome of the Drosophila fly brain, single-cell RNA sequencing and genetic manipulations

Objective

Several neurodevelopmental disorders such as autism spectrum disorder and schizophrenia have their roots in aberrant circuit formation. Hence, understanding the principles underlying neuronal connectivity bears fundamental implications for the treatment of these diseases. However, these principles are not well understood, partly due to the lack of information about how developmental processes affect connectivity. While previous research has primarily relied on the study of wiring genes, it has become increasingly clear that expression of these alone cannot explain circuit formation, and hence developmental time (i.e. when neurons are born) is likely to play an important role. To address the role of developmental time in circuit formation, I will perform the first comprehensive study of how birth date relates to connectivity in an entire neuronal structure. To do so, I will use the genetically accessible Drosophila visual system and study how neurons generated at the same time from two different progenitor regions connect to each other during development. I will use cutting-edge single-cell RNA sequencing of one of these regions at neurogenesis stages to determine the identity of the neurons generated and their birth order. Taking advantage of the existing whole fly brain connectome, I will identify their synaptic partners from the other progenitor region, for which the birth order is known. Performing precise genetic manipulations to uncouple birth date and molecular identity, I will address the role of both components in correct partner matching. Moreover, I will generate the first scRNA-seq datasets of Musca domestica and Aedes aegypti visual systems during neurogenesis and perform circuit mapping to determine whether the mechanisms uncovered in Drosophila are conserved. This ambitious project will shed light into the mechanisms of circuit connectivity during development and evolution, likely providing insights into the regulators that go awry in disease.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
Net EU contribution

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€ 195 914,88
Address
RUE MICHEL ANGE 3
75794 PARIS
France

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Ile-de-France Ile-de-France Paris
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Research Organisations
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