Theses Doctoral

Detection of respiratory gas levels by internal sensory neurons in Drosophila larvae

Lu, Shan

Internal sensory neurons monitor the chemical and physical state of the body, providing critical information to the nervous system for maintaining homeostasis and survival. Across species, such neurons innervate visceral organs to detect and relay information about their chemical and physical state to the central nervous system (CNS). While electrophysiology experiments over several decades have revealed a wide of range of stimuli that can activate internal sensory neurons, how stimuli are detected at the cellular and molecular level is only beginning to be elucidated. To elucidate the cellular and molecular basis of chemosensation by internal neurons, I used a population of larval Drosophila sensory neurons, tracheal dendrite (td) neurons, as the model system for my thesis work.I first presented a detailed characterization of the morphology of td neurons and their association with the tracheal system. I found that td dendrites extend along tracheal epithelial cells across their whole length. I further described that td dendrites extend to tracheal fusion sites, and can be observed terminating as enlarged bulbs adjacent to the tube enlargements. This specialized structure formed by td dendrites in relation to the nearby tracheal tissues may serve as an end organ for td sensory functions.

I then proceeded to test the sensory functions of the td neurons. I found that td neurons respond to respiratory gases, namely decreases in O2 levels and increases in CO2 levels. Furthermore, I assessed the roles of atypical soluble guanylyl cyclases (Gycs) and a gustatory receptor (Gr) in mediating these responses. I found that Gyc88E/Gyc89Db are necessary for td responses to hypoxia, and that Gr28b is necessary for td responses to CO₂. Rescue of Gr28b isoform c rescued the mutant phenotype and also generalized the response to CO₂ in the td network. Additionally, I presented data suggesting carbonic anhydrases from surrounding tissues are required for td responses to CO₂, further elucidating the sensory transduction pathway of internal CO₂ detection.

I further showed that gas-sensitive td neurons are activated when larvae burrow for a prolonged duration, demonstrating a natural-like feeding condition in which td neurons are activated. I also found that Drosophila larvae tend to avoid their td neurons being activated, suggesting td activation is aversive to the animals.

Together, my work identified two stimuli that are detected by partially overlapping subsets of internal sensory neurons, and established roles for Gyc88E/Gyc89Db in the detection of hypoxia, and Gr28b together with carbonic anhydrases in the detection of CO₂. Combined with our previous understanding, different td neurons express various combinations of chemosensory receptors and have distinct functions, some of which remain to be discovered, indicating that this is a multifunctional internal sensory system.

In conclusion, the results I presented in my thesis established new sensory detection pathways of Drosophila larval internal sensory neurons, which may be generalized across species and facilitate understanding of internal sensory systems.


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More About This Work

Academic Units
Biological Sciences
Thesis Advisors
Grueber, Wesley B.
Ph.D., Columbia University
Published Here
January 18, 2023