The Sex-lethal gene occupies a central position in the developmental pathway controlling sexual dimorphism in the fly. The special importance of Sxl in this pathway my be understood by considering the three central themes in developmental biology: initiation, determination, and differentiation. Sxl is unusual amongst know developmental loci in that it plays a critical role in all three of these processes. It is involved in the initial choice between female and male somatic development. This choice is made early in development in response to the X/A ratio. In females (2X/2A), Sxl is turned on by a complex process which begins with the transcriptional activation of a special embryonic Sxl promoter. The protein products of RNAs produced by this embryonic promoter then set an Sxl autoregulatory feedback loop in motion. This autoregulatory feedback loop is at the level of RNA splicing and its functions to maintain a stable commitment to the female pathway throughout the remainder of development. Sxl also ensures that subsequent steps in the sexual pathway are properly executed by directing the female splicing of downstream genes. Male (1X/2A) development is selected by keeping the Sxl gene off and the male pathway is then maintained and executed by default. The goal of the research proposed here is to understand how Sxl functions in pathway initiation and pathway maintenance at the molecular level.
