The mode of action of Fruitless: Is it an easy matter to switch the sex?

Genes Brain Behav. 2020 Feb;19(2):e12606. doi: 10.1111/gbb.12606. Epub 2019 Sep 5.


The fruitless (fru) locus was originally defined by a male sterile mutation that promotes male-to-male courtship while suppressing male-to-female courtship in Drosophila melanogaster. The fru promoter-1 pre-RNA generates a set of BTB-zinc finger family FruM proteins expressed exclusively in the male neurons, leading to the formation of sexual dimorphisms in neurons via male-specific neuroblast proliferation, male-specific neural survival, male-specific neuritegenesis or male-specific arbor patterning. Such a wide spectrum of phenotypic effects seems to result from chromatin modifications, in which FruBM recruits Bonus, Histone deacetylase 1 (HDAC1) and/or Heterochromatin protein 1a (HP1a) to ~130 target sites. One established FruBM transcriptional target is the axon guidance protein gene robo1. Multiple transcriptional regulator-binding sites are nested around the FruBM-binding site, and mediate sophisticated modulation of the repressor activity of FruBM. FruBM also binds to the Lola-Q transcriptional repressor to protect it from proteasome-dependent degradation in male but not female neurons as FruBM exists only in male neurons, leading to the formation of sexually dimorphic neural structures. These findings shed light on the multilayered network of transcription regulation orchestrated by the master regulator FruBM.

Keywords: Drosophila; RNA polymerase II; axon guidance; chromatin remodeling; courtship behavior; neuritegenesis; sexually dimorphic neurons; the fruitless gene; transcription factor; ubiquitin-proteasome pathway.

Publication types

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

MeSH terms

  • Animals
  • Courtship / psychology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / metabolism
  • Female
  • Histone Deacetylase 1 / metabolism
  • Male
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology*
  • Neurons / metabolism
  • Promoter Regions, Genetic / genetics
  • Receptors, Immunologic / genetics
  • Sex Characteristics
  • Sex Determination Processes / genetics*
  • Sex Determination Processes / physiology
  • Sexual Behavior, Animal / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors / physiology*


  • Drosophila Proteins
  • Nerve Tissue Proteins
  • Receptors, Immunologic
  • Transcription Factors
  • fru protein, Drosophila
  • HDAC1 protein, Drosophila
  • Histone Deacetylase 1