Cellular Signaling Pathways Regulate Nociceptor Sensitivity To Noxious Stimuli In Drosophila Melanogaster Larvae

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Adam Willits (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/
Advisor
Andrew Bellemer

Abstract: Chronic pain is a major public health concern that affects about 100 million Americans, generates $600 billion in healthcare costs, and is a major cause of missed work. For these reasons, it is important to research the cellular mechanisms of sensory neuron function in order to develop more effective clinical interventions. To better understand chronic pain, Drosophila melanogaster was used to investigate sensory neuron function. The major goal of this thesis was to understand the cellular signaling mechanisms that control sensory neuron sensitivity. In one project, flies lacking the function of the G protein signaling genes, Gaq and norpA, were studied. These genes are involved in neurotransmitter signaling and electrical excitability, and the results showed that both are required for behavioral responses to harsh thermal and mechanical stimuli. Removal of their function does not result in morphological differences in the sensory neurons that detect harsh stimuli, which suggests that they are involved in signaling in these neurons instead of their development. In a second study, another gene called off-track 2 (otk2), which encodes a transmembrane receptor that is involved in the Wnt signaling pathway in Drosophila, was targeted. Loss-of-function of otk2 showed that it plays a role in sensory neurons in the detection of harsh thermal stimuli but not harsh mechanical stimuli. In addition, loss of otk2 function results in a tiling defect where the dendrites of sensory neurons overlap with the dendrites of neighboring neurons of the same class. In order to determine if Otk2 and either Frizzled or Frizzled2 are functionally coupled to activate Wnt signaling, loss-of-function experiments on fz and fz2 were conducted. Loss-of-function of fz did not result in a defect in either thermal or mechanical nociception, while loss-of-function of fz2 caused a defect in a noxious thermal behavioral assay. Otk2 and Fz2 have been shown previously to physically interact. The data in this study suggests that otk2 and fz2 are functionally coupled in an inhibitory mechanism to regulate sensory neuron sensitivity. A potential mechanism of action for these receptors could be regulating sensory neuron function through the developmental control of dendrite outgrowth.

Additional Information

Publication
Thesis
Willits, A. (2019). Cellular Signaling Pathways Regulate Nociceptor Sensitivity To Noxious Stimuli In Drosophila Melanogaster Larvae. Unpublished Master’s Thesis. Appalachian State University, Boone, NC.
Language: English
Date: 2019
Keywords
Drosophila, Nociception, G protein signaling cascade, Wnt signaling

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