Figure 7

A proposed landscape of cross-antagonism between opioid and pheromone signaling under different growth conditions. Under a fed state (left), TGF-β, insulin, and serotonergic signaling might be in ‘active state’, which maintained the moderate expression levels of nlp-24 and NPR-17, making normal pharyngeal pumping rate. Since DAF-16 and SKN-1 might not be activated, pheromone actions (e.g., ascr#2) were unlikely active. Under STS (middle), the opioid signaling mediated by activated nlp-24 expression might occur autonomously with concomitant activation of pharyngeal pumping, which might also cause GPA-3 to interact with NPR-17. When encountered with sudden stress (e.g., increased population density) (right), pheromone ascr#2 would bind to seemingly DAF-37 (and GPA-3), which might subsequently suppress TGF-β signaling, but NHR-69, a downstream factor of TGF-β signaling, might be activated and then suppress the nlp-24 expression (see also Fig. 6e,f). Under LTS, SKN-1a would be activated and then likely bound to one of putative promoter regions (e.g., binding region I, see also Supplementary Fig. S7) as a negative transcription factor. Together, this might culminate in attenuation of the opioid signaling but stimulation of the pheromone-mediated dauer entry to facilitate stress avoidance.