The primary sex determination signal of Drosophila acts at the level of transcription.

For Drosophila, the choice between male and female development is made by the switch gene, Sxl, in response to the X:A ratio. Once Sxl is turned on in females, it actively maintains the determined state, independent of the X:A signal, by a positive autoregulatory feedback loop in which Sxl proteins direct the female-specific splicing of Sxl transcripts. In this paper we have investigated the mechanism controlling pathway initiation. Our results suggest a two-step model for the initial activation of Sxl in females. In the first step, a special class of Sxl mRNAs is expressed in female embryos from an early promoter that responds to the genes signaling the X:A ratio. The proteins produced from these early mRNAs then initiate the autoregulatory loop by directing the female-specific processing of transcripts from the late Sxl promoter.