xol-1 acts as an early switch in the C. elegans male/hermaphrodite decision

xol-1 is the earliest-acting gene in the known hierarchy that controls C. elegans sex determination and dosage compensation. We show that the primary sex-determining signal (the X/A ratio) directs the choice of sexual fate by regulating xol-1 transcript levels: high xol-1 expression during gastrulation triggers male development, whereas low expression at that time permits hermaphrodite development. Inappropriately high xol-1 expression causes hermaphrodites to activate the male program of development and die from a disruption in dosage compensation. These results demonstrate that xol-1 functions as an early developmental switch to set the choice of sexual fate and suggest that assessment of the X/A ratio occurs only early in embryogenesis to determine sex. Moreover, sdc-2, a gene that must be repressed by xol-1 to ensure male development, may be a direct target of negative regulation by xol-1.