Summary
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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| Web resources: | https://cordis.europa.eu/project/id/101154260 |
| Start date: | 01-05-2024 |
| End date: | 30-04-2026 |
| Total budget - Public funding: | - 195 914,00 Euro |
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Original description
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.Status
SIGNEDCall topic
HORIZON-MSCA-2023-PF-01-01Update Date
23-12-2024
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