Pheromone-dependent olfaction bidirectionally regulates muscle extracellular vesicles formation

Abstract

Extracellular vesicles (EVs) are involved in multiple biological processes; however, there is limited knowledge of the influence of environmental factors or other individuals in a population on EV-regulated systems. The largest evolutionarily conserved EVs, exophers, are a component of the C. elegans maternal somatic tissue resource management system induced by embryos developing in utero, and thus progeny of individuals with active exopher biogenesis (exophergenesis) appear to be privileged. Using this model, we investigated the inter-tissue and social regulatory mechanisms of exophergenesis. We found that the predominant male pheromone, ascr#10, increases exopher production in hermaphrodites via the G-protein-coupled receptor STR-173 in the ASK sensory neurons. In contrast, pheromones from other hermaphrodites in the population temper exophergenesis. Within the hermaphrodite, an increase in embryo accumulation drives pro-exopher signals, and the internal sensory neurons AQR, PQR, and URX play a central role in modulating exopher levels. This intricate process is regulated partly via the neuropeptides FLP-8 and FLP-21, which originate from the URX and AQR/PQR/URX neurons, respectively. Our results reveal a regulatory network integrating internal and external cues, including control of somatic EVs production by the nervous system in response to social signals.