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.

性分化由整个动物王国的不同主要调节因素控制。转录因子 TRA-1 是线虫秀丽隐杆线虫 体细胞性别分化的主要调节因子，据报道它在雌雄同体的非性腺体细胞中具有性别特异性表达。使用gfp标记的tra-1等位基因，我们在五个维度上揭示了 TRA-1 蛋白表达的意外动态：空间、时间、性别、环境和亚细胞定位。我们显示了体细胞组织中 TRA-1 蛋白积累的时间调节，在不同组织类型中具有不同的表达开始，表明性别认同不是统一施加的。在雌雄同体中，神经元表达最初受到高度限制，然后在幼虫发育期间在个体之间可变地增加，直到在第四个幼虫阶段达到全神经元表达。出乎意料的是，TRA-1 也在雄性性共享神经元的一个子集中积累。此外，需要食物信号来开启肠道中的 TRA-1 表达，而环境压力因素会关闭整个非性腺体细胞中的 TRA-1 表达，表明体细胞的性别分化可能受到外部条件的影响。我们表明，与控制成人 TRA-1 积累的蛋白质降解机制相反，发育过程中 TRA-1 积累的时间、性别和空间特异性受到转录调控。一种核激素受体，daf-12以前与秀丽隐杆线虫的发育时间有关，有助于神经系统中 TRA-1 的时间积累。我们的研究揭示了性身份获得的马赛克和动态性质，并揭示了大脑性别分化的激素控制机制。