Corazonin neuroendocrine pathway orchestrates stress-associated physiology in Drosophila

Environmental factors challenge the physiological homeostasis in animals, thereby evoking stress responses. Various mechanisms have evolved to counter stress at the organism level, including regulation by neuropeptides. Corazonin (Crz) is a neuropeptide known to regulate stress-associated physiology in Drosophila. However, the neural circuits and hormonal pathways underlying this regulation are poorly known. To unveil targets of Crz, we mapped the Crz receptor (CrzR) expression in Drosophila central nervous system (CNS). The CrzR is expressed in peptidergic neurons in the adult CNS, including the median neurosecretory cells and certain clock neurons in the brain, Hugin neurons in the subesophageal zone (SEZ) and CAPA-expressing neurosecretory cells in the SEZ and abdominal neuromeres (Va neurons). We focused on the Va neurons since they produce osmoregulatory peptides (CAPA-1 and CAPA-2), which mediate recovery from desiccation and cold stress. Trans-Tango labeling to determine synaptic partners failed to reveal connections between Crz and Va neurons, suggesting hormonal interactions. To validate the signaling between Crz and Va neurons, we show that knockdown of Crz in Crz-producing neurons and CrzRin Va neurons increases survival under desiccation and delays chill coma recovery. Moreover, immunolabeling data suggests that Crz is released under nutritional and osmotic stress, and in vivo Crz peptide injections influence responses to desiccation and chill coma. Thus, Crz modulates Va neurons to maintain osmotic/ionic homeostasis, which in turn influences stress tolerance. Taken together with previous data, we propose that Crz acts via both the fat body and peptidergic neurons in the CNS to regulate stress-associated physiology.