Respiratory epithelia in vertebrates: sites of chemosensing and neurogenesis

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The control of breathing and uptake of oxygen by respiratory organs (e.g. lungs, gills and skin) is important to all vertebrates for survival. Specialized cells, called oxygen chemoreceptors, detect low oxygen in the blood or environment (called "hypoxia") and initiate a cascade of events that ultimately leads to physiological changes in respiratory rate and cardiovascular function. While many studies have described these cells in mammals, oxygen chemoreceptors are poorly defined in aquatic vertebrates, such as fish. This Discovery Grant application proposes research to fill these voids and to: (i) Identify a metabolic link between the "sensing" of oxygen within chemoreceptors and their ability to transmit signals to the nervous system; (ii) Determine the chemical interactions between chemoreceptors and sensory neurons; and (iii) Define the basic properties of gill regeneration and the role of hypoxia in chemoreceptor proliferation. The proposed experiments will utilize a transgenic line of the model vertebrate, the zebrafish, in which oxygen chemoreceptors of the gills and skin are conveniently labelled by a green fluorescent marker. We will perform sensitive electrophysiological recording at the level of membrane ion channels, imaging of intracellular calcium, and high-resolution confocal microscopy. This research program will employ an average of five graduate students and three undergraduate students per year over a five-year period. Our work will constitute significant advances in the fields of Oxygen Sensing, Neuroscience, Development and Comparative Physiology. Our studies may redefine working models of respiratory control in all vertebrates, and will be important for understanding the impact of climate change on aquatic species, which profoundly affects the length and frequency of hypoxic events in aquatic environments. The proposed research may therefore lead to major environmental and economic impact.