Developing zebrafish utilize taste-signaling pathways for oxygen chemoreception

A fundamental requirement for all animals is to sense and respond to changes in environmental O₂ availability. Low O₂ (hypoxia) typically stimulates breathing, a universal and critical response termed the hypoxic ventilatory response (HVR). In this study, we test the hypothesis that taste-signaling pathways are used for O₂ sensing and activation of the HVR. We show that Merkel-like cells (MLCs), which are part of the taste-bud complex, function as O₂ chemoreceptor cells in larval zebrafish and that transduction of the O₂ signal uses taste-signaling pathways. Specifically, MLCs responded to hypoxia in vivo with an increase in Ca²⁺ activity that can drive the HVR. In addition, MLCs transmit O₂ signals to afferent cranial nerves IX and X (nIX/X), which project into the area postrema within the hindbrain and synapse with interneurons that are in contact with vagal motor neurons. Hypoxia or chemo-activation of nIX/X caused Ca²⁺ activity to increase within the area postrema and elicited hyperventilation. The results provide the first demonstration of an O₂ signaling pathway that commences with the activation of taste receptors (MLCs) to yield a critical physiological reflex, the HVR.