title: Isoform-specific control of male neuronal differentiation and behavior in Drosophila by the fruitless gene.
abstract: BACKGROUND
  How the central nervous system (CNS) develops to implement innate behaviors remains largely unknown. Drosophila male sexual behavior has long been used as a model to address this question. The male-specific products of fruitless (fru) are pivotal to the emergence of this behavior. These putative transcription factors, containing one of three alternative DNA binding domains, determine the neuronal substrates for sexual behavior in male CNS.
  
  
  RESULTS
  We isolated the first fru coding mutation, resulting in complete loss of one isoform. At the neuronal level, this isoform alone controls differentiation of a male-specific muscle and its associated motorneuron. Conversely, a combination of isoforms is required for development of serotonergic neurons implicated in male copulatory behavior. Full development of these neurons requires the male-specific product of doublesex, a gene previously thought to act independently of fru. At the behavioral level, missing one isoform leads to diminished courtship behavior and infertility. We achieved the first rescue of a distinct fru behavioral phenotype, expressing a wild-type isoform in a defined subset of its normal expression pattern.
  
  
  CONCLUSIONS
  This study exemplifies how complex behaviors can be controlled by a single locus through multiple isoforms regulating both developmental and physiological pathways in different neuronal substrates.
authors.affiliation: IBLS Division of Molecular Genetics, University of Glasgow, Glasgow G11 6NU, United Kingdom.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Billeter
authors.forename: Adriana
authors.initials: A
authors.lastname: Villella
authors.forename: Jane B
authors.initials: JB
authors.lastname: Allendorfer
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Dornan
authors.forename: Michael
authors.initials: M
authors.lastname: Richardson
authors.forename: Donald A
authors.initials: DA
authors.lastname: Gailey
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Goodwin
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D005298:Fertility; D018507:Gene Expression Regulation, Developmental; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; C070369:DSX protein, Drosophila; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C103226:fru protein, Drosophila