Sexual dimorphism in the nervous system: Three principles from the nematode C.elegans

Recent interest in the neurobiology of the C. elegans male has driven exciting progress in understanding sexual dimorphism in the nervous system of this important model system. From these studies, a framework emerges in which the effects of biological sex fall into three overlapping categories. First, sex modulates developmental programs of cell lineage, neurogenesis, and cell fate specification to generate neuronal classes and structures that appear only in one sex. Second, sex modifies synaptic connectivity to alter the topology of neural circuits. Third, sex acts as a dimension of internal state, developmentally and dynamically modulating the physiology of sex-shared neurons and circuits. Together, these effects program sex-specific behaviors, tune sex-shared behaviors, and implement sexually dimorphic behavioral plasticity. Importantly, C. elegans offers the opportunity to understand these effects with uniquely high mechanistic resolution. Although mechanisms of sex determination differ markedly by species, these principles are likely conserved across evolution.