Temporal, Spatial, Sexual and Environmental Regulation of the Master Regulator of Sexual Differentiation in C. elegans.

Sexual differentiation is controlled by diverse master regulatory factors across the animal kingdom. The transcription factor TRA-1 is the master regulator of somatic sexual differentiation in the nematode C. elegans, where it was reported to be expressed sex-specifically in the non-gonadal soma of hermaphrodites. Using a gfp-tagged allele of tra-1. we reveal unanticipated dynamics of TRA-1 protein expression in five dimensions: space, time, sex, environment, and subcellular localization. We show temporal regulation of TRA-1 protein accumulation in somatic tissues with different onsets of expression in different tissue types, indicating that sexual identity is not uniformly imposed. In hermaphrodites, neuronal expression is initially highly restricted and then increases variably between individuals during larval development until reaching panneuronal expression in the fourth larval stage. Unexpectedly, TRA-1 also accumulates in a subset of sex-shared neurons in the male. Additionally, a food signal is required to turn on TRA-1 expression in the intestine, and environmental stressors shut off TRA-1 expression in the entire non-gonadal soma, suggesting that somatic sexual differentiation may be affected by external conditions. We show that, in contrast to the protein degradation mechanisms that control TRA-1 accumulation in the adult, the temporal, sexual, and spatial specificities of TRA-1 accumulation during development are regulated transcriptionally. A nuclear hormone receptor, daf-12, previously implicated in developmental timing in C. elegans, contributes to temporal accumulation of TRA-1 in the nervous system. Our studies reveal a mosaic and dynamic nature of sexual identity acquisition and uncover hormonal control mechanisms for sexual differentiation of the brain.