Genetic control of sex differences in C. elegans neurobiology and behavior

As a well-characterized, genetically tractable animal, the nematode Caenorhabditis elegans is an ideal model to explore the connections between genes and the sexual regulation of the nervous system and behavior. The two sexes of C. elegans, males and hermaphrodites, have precisely defined differences in neuroanatomy: superimposed onto a "core" nervous system of exactly 294 neurons, hermaphrodites and males have 8 and 89 sex-specific neurons, respectively. These sex-specific neurons are essential for cognate sex-specific behaviors, including hermaphrodite egg-laying and male mating. In addition, regulated sex differences in the core nervous system itself may provide additional, though poorly understood, controls on behavior. These differences in the nervous system and behavior, like all known sex differences in the C. elegans soma, are controlled by the master regulator of C. elegans sex determination, tra-1. Downstream of tra-1 lie specific effectors of sex determination, including genes controlling sex-specific cell death and a family of regulators, the DM-domain genes, related to Drosophila doublesex and the vertebrate DMRT genes. There is no central (i.e., gonadal) regulator of sexual phenotype in the C. elegans nervous system; instead, tra-1 acts cell-autonomously in nearly all sexually dimorphic somatic cells. However, recent results suggest that the status of the gonad can be communicated to the nervous system to modulate sex-specific behaviors. Continuing research into the genetic control of neural sex differences in C. elegans is likely to yield insight into conserved mechanisms of cell-autonomous cross talk between cell fate patterning and sexual differentiation pathways.