Dynamic, Non-binary Specification of Sexual State in the C. elegans Nervous System

Biological sex in animals is often considered a fixed, individual-level characteristic, However, not all sex-specific features are static: for example, C. elegans males (XO) can sometimes exhibit hermaphrodite (XX)-like feeding behavior [1, 2]. (C. elegans hermaphrodites are somatic females that transiently produce self-sperm.) Essentially all somatic sex differences in C. elegans are governed by the master regulator tra-1, whose activity is controlled by chromosomal sex and is necessary and sufficient to specify the hermaphrodite state [3]. One aspect of this state is high expression of the chemoreceptor odr-10. In hermaphrodites, high odr-10 expression promotes feeding, but in males, low odr-10 expression facilitates exploration [4]. However, males suppress this sex difference in two contexts: juvenile males exhibit high odr-10 expression and food deprivation activates odr-10 in adult males [4-6]. Remarkably, we find that both of these phenomena require tra-1. In juvenile (L3) males, tra-1 is expressed in numerous neurons; this expression diminishes as individuals mature into adulthood, a process that requires conserved regulators of sexual maturation. tra-1 remains expressed in a small number of neurons in adult males, where it likely has a permissive role in odr-10 activation. Thus, the neuronal functions of tra-1 are not limited to hermaphrodites; rather, tra-1 also acts in the male nervous system to transiently suppress a sexual dimorphism, developmentally and in response to nutritional stress. Our results show that the molecular and functional representation of sexual state in C. elegans is neither static nor homogeneous, challenging traditional notions about the nature of biological sex.