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 WA 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 WA 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.