Sxl

Sxl, short for Sex-lethal, is a gene on the X chromosome of Drosophila melanogaster that encodes an RNA-binding protein acting as a master regulator of sex determination and dosage compensation. The gene is expressed from two promoters, producing transcripts that are differentially regulated during development. In XX (female) embryos, the X chromosome to autosome ratio activates Sxl expression from the early promoter, leading to the production of functional Sxl protein. In XY (male) embryos, Sxl expression remains low or absent, causing the male developmental program to proceed.

The Sxl protein contains RNA recognition motif domains and functions primarily at the level of RNA processing. It regulates alternative splicing and, in some cases, translation of several downstream targets, most notably transformer (tra), doublesex (dsx), and msl-2. By promoting female-specific splicing of tra, Sxl drives the production of the female-specific Tra protein, which in turn regulates dsx splicing to yield the DSX-F transcription factor that supports female development. Conversely, in the absence of Sxl activity, tra is not properly activated, leading to DSX-M and male development. Sxl also inhibits translation of msl-2 in females, preventing the assembly of the dosage compensation complex on the X chromosome.

Autoregulatory feedback maintains Sxl expression in XX individuals, ensuring a stable female development pathway. Sxl is a quintessential example of a sex-determination cascade based on alternative splicing. Although central to Drosophila, Sxl has no direct, conserved homolog with identical function in vertebrates.