A Developmental Framework for Coupling Neurogenesis to Circuit Formation in Drosophila
| dc.contributor.advisor | Doe, Chris | |
| dc.contributor.author | Mark, Brandon | |
| dc.date.accessioned | 2020-02-27T22:39:01Z | |
| dc.date.available | 2020-02-27T22:39:01Z | |
| dc.date.issued | 2020-02-27 | |
| dc.description.abstract | Two central questions in neuroscience are how the brain is capable of both generating the diversity of neurons necessary for generating appropriate behaviors and how developmental programs are capable of then wiring these diverse populations of neurons together into functional circuits. While a great deal of progress has been made towards understanding the mechanisms that specify neuronal diversity, it is less clear how these mechanisms might also regulate neuronal morphology and connectivity. In this dissertation, we identified a novel mechanism for diversity generation in the Drosophila central brain. Next, we mapped the developmental origins of seven lineages in the Drosophila ventral nerve cord into a serial-section electron microscopy (SSEM) volume and used this connectome to examine how lineage, hemilineage, and birth order correlate with synaptic targeting and connectivity. Finally, we combined the same SSEM volume with single-muscle calcium imaging to explore how these functional circuits are capable of generating distinct locomotor behaviors. In chapter two, we show that the hormone ecdysone is required to down-regulate early neuroblast temporal identity factors as well as activate later temporal identity factors. This is the first example of hormonal regulation of temporal factor expression in Drosophila embryonic or larval neural progenitors. In chapter three, we map the developmental origin of neurons from seven neuroblasts and identify each neuron within a complete EM reconstruction of the Drosophila larval CNS. We find that lineages generate a sensory and motor processing hemilineage in a notch-dependent manner. Within each hemilineage, we observe a birth order dependent “tiling” of the neuropil, and neurons with similar temporal identity are enriched for shared connectivity. Thus, diversity generating mechanisms progressively restrict neuropil targeting, synapse localization, and connectivity. In chapter four, we characterize neural circuits generating Drosophila forward and backward locomotion. We show that a subset of MNs change recruitment timing for each behavior. Next, we used a SSEM volume to reconstruct a comprehensive larval PMN-MN connectome. We conclude that different locomotor behaviors are generated by multiple mechanisms: muscle recruitment differences, dedicated PMN/MN connectivity; asymmetric PMN/MN morphology, and behavior-specific PMN activity. This dissertation contains unpublished co-authored material. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/25288 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | All Rights Reserved. | |
| dc.subject | Connectomics | en_US |
| dc.subject | Development | en_US |
| dc.subject | Drosophila | en_US |
| dc.title | A Developmental Framework for Coupling Neurogenesis to Circuit Formation in Drosophila | |
| dc.type | Electronic Thesis or Dissertation | |
| thesis.degree.discipline | Department of Biology | |
| thesis.degree.grantor | University of Oregon | |
| thesis.degree.level | doctoral | |
| thesis.degree.name | Ph.D. |
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