Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila

Cell. 1991 Apr 19;65(2):229-39. doi: 10.1016/0092-8674(91)90157-t.


Sex-lethal is a binary switch gene that controls all aspects of Drosophila sexual dimorphism. It must be active in females and inactive in males. The on/off regulation reflects alternative RNA splicing in which full-length proteins are produced only in females. Here we investigate the role of Sxl in maintaining sexual pathway commitments. By ectopic expression of a female Sxl cDNA in transgenic male flies, we show that Sxl protein induces a rapid switch from male- to female-specific splicing. The ectopically expressed Sxl protein wil trans-activate an endogenous wild-type Sxl gene. This establishes a feedback loop in which Sxl proteins induce their own synthesis by directing the female-specific splicing of Sxl transcripts. We conclude that the female determined state is maintained by Sxl through positive autoregulation, while the male determined state is maintained by default.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Animals
  • Drosophila / genetics*
  • Drosophila Proteins*
  • Female
  • Gene Expression Regulation*
  • Genes, Switch*
  • Homeostasis
  • Insect Hormones / analysis
  • Insect Hormones / genetics
  • Insect Hormones / physiology
  • Male
  • Mutation
  • Phenotype
  • Polymerase Chain Reaction / methods
  • RNA Splicing*
  • RNA-Binding Proteins*
  • Restriction Mapping
  • Sex Determination Analysis*
  • Transcription, Genetic
  • Transcriptional Activation
  • Transformation, Genetic*


  • Drosophila Proteins
  • Insect Hormones
  • RNA-Binding Proteins
  • Sxl protein, Drosophila