Development and organization of the Drosophila olfactory circuit
Abstract/Contents
- Abstract
- The formation of complex but highly organized neural circuits requires precise recognition and interactions between cells that constitute the nervous system. A growing body of research has discovered numerous neuro-neuronal interactions underlying neural development, while the important roles played by glia are appreciated only more recently. In this thesis, I utilized the olfactory circuit of Drosophila melanogaster as a model to study the roles of both neurons and glia which together establish the unique structure of the olfactory system. During the assembly of the Drosophila olfactory circuit, ~50 olfactory receptor neuron (ORN) classes and ~50 projection neuron (PN) classes form one-to-one synaptic connections in ~50 glomerular compartments in the antennal lobe, each of which represents a discrete olfactory information processing channel. Several cell surface molecules have been reported to mediate neuro-neuronal interactions and determine the specific connectivity of olfactory neurons. However, we are still far from a complete understanding of this process. In a genetic screen to look for additional wiring molecules in this process, I identified Fish-lips (Fili), a leucine-rich repeat transmembrane protein, to be expressed in a subset of olfactory neurons. Loss- and gain-of-function experiments indicate that Fili can instruct PN dendrites to project to proper glomerular targets. Besides olfactory neurons, the antennal lobe is also permeated by several types of glia. Specifically, each glomerular compartment is separated from the adjacent compartments by membranous processes from the ensheathing glia. In a genetic screen designed to reveal molecular mechanisms underlying glia morphogenesis, I identified that Thisbe, a fibroblast growth factor released from olfactory neurons particularly local interneurons (LNs), controls ensheathing glia to wrap each glomerulus. The FGF receptor, Heartless, acts cell-autonomously in ensheathing glia to regulate process elaboration so as to insulate each neuropil compartment. Overexpressing Thisbe in ORNs or PNs causes over-wrapping of glomeruli to which their axons or dendrites target. Failure to establish the FGF-dependent glia structure disrupts precise ORN axon targeting and discrete glomerular formation. In summary, I have identified two molecular mechanisms underpinning the assembly of the olfactory circuit. Fili, combined with previously identified cell surface cues, can define dendrites from different PN classes and instruct them to target correct glomeruli. After the initial innervation of PN dendrites and ORN axons, ensheathing glia respond to a neuronal cue, Thisbe, to pattern the boundaries of the nascent glomerular compartments; neural compartments in turn require such glial barriers to separate themselves from neighboring compartments, so as to ensure the correct organization of the olfactory circuit. These findings highlight the synergism of neurons and glia in shaping the intricate network of the nervous system.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Wu, Bing | |
|---|---|---|
| Associated with | Stanford University, Department of Biology. | |
| Primary advisor | Luo, Liqun, 1966- | |
| Thesis advisor | Luo, Liqun, 1966- | |
| Thesis advisor | Clandinin, Thomas R. (Thomas Robert), 1970- | |
| Thesis advisor | Shen, Kang, 1972- | |
| Thesis advisor | Südhof, Thomas C | |
| Advisor | Clandinin, Thomas R. (Thomas Robert), 1970- | |
| Advisor | Shen, Kang, 1972- | |
| Advisor | Südhof, Thomas C |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Bing Wu. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Bing Wu
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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