Neuronal Nrf/SKN-1B controls a sexually dimorphic neuroendocrine pathway for C. elegans exploratory behaviour.

The SKN-1/Nrf transcription factor family is integral to metabolic homeostasis. There are three SKN-1 isoforms in Caenorhabditis elegans, each with different functions. One of these, SKN-1B, is expressed specifically in neurons and controls hermaphrodite behaviour in response to food. In a laboratory environment C. elegans hermaphrodites must allocate energy efficiently between exploratory food-seeking behaviour, reproduction, and survival, whereas males have to balance both food-seeking with mate-seeking exploratory behaviours. Here, we evaluate the role of SKN-1B in male behaviour and show that SKN-1B acts in a sexually dimorphic manner to control exploratory behaviour, mitochondrial morphology, and mitochondrial function. Moreover, we show that SKN-1B is expressed in a sexually dimorphic pattern, and that SKN-1B influences gene expression on a much broader scale in males compared to hermaphrodites. This analysis identified a neuronal signalling pathway, specifically in males between SKN-1B, the TGF-β ligand DAF-7 and the chemosensory regulator ODR-10, and that this pathway contributes to increased exploratory behaviour in skn-1b mutant males. Taken together our findings identify SKN-1B as a sex-specific neuronal switch to control food searching and mating behaviours. Sexual dimorphism is essential for optimizing survival and reproductive success and our findings establish SKN-1B as a regulator of sex-specific behavioural and metabolic traits. This work provides new insights into neuronal regulation of metabolism and behaviour, with implications for sex-specific physiological adaptations in other species.