Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system.
BACKGROUND
In Drosophila, male courtship behavior is regulated in large part by the gene fruitless (fru). fru encodes a set of putative transcription factors that promote male sexual behavior by controlling the development of sexually dimorphic neuronal circuitry. Little is known about how Fru proteins function at the level of transcriptional regulation or the role that isoform diversity plays in the formation of a male-specific nervous system.


RESULTS
To characterize the roles of sex-specific Fru isoforms in specifying male behavior, we generated novel isoform-specific mutants and used a genomic approach to identify direct Fru isoform targets during development. We demonstrate that all Fru isoforms directly target genes involved in the development of the nervous system, with individual isoforms exhibiting unique binding specificities. We observe that fru behavioral phenotypes are specified by either a single isoform or a combination of isoforms. Finally, we illustrate the utility of these data for the identification of novel sexually dimorphic genomic enhancers and novel downstream regulators of male sexual behavior.


CONCLUSIONS
These findings suggest that Fru isoform diversity facilitates both redundancy and specificity in gene expression, and that the regulation of neuronal developmental genes may be the most ancient and conserved role of fru in the specification of a male-specific nervous system.
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK. Electronic address: megan.goodwin@dpag.ox.ac.uk.
Megan C
MC
Neville
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
Tetsuya
T
Nojima
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
Elizabeth
E
Ashley
Centre for Biological Diversity, University of St Andrews, St Andrews, KY16 9TH, UK.
Darren J
DJ
Parker
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
John
J
Walker
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Tony
T
Southall
Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium.
Bram
B
Van de Sande
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK.
Ana C
AC
Marques
Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Bettina
B
Fischer
The Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Andrea H
AH
Brand
Cambridge Systems Biology Centre, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Steven
S
Russell
Centre for Biological Diversity, University of St Andrews, St Andrews, KY16 9TH, UK.
Michael G
MG
Ritchie
Laboratory of Computational Biology, Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium.
Stein
S
Aerts
Department of Physiology, Anatomy and Genetics, University of Oxford, Sherrington Building, Parks Road, Oxford OX1 3PT, UK. Electronic address: stephen.goodwin@dpag.ox.ac.uk.
Stephen F
SF
Goodwin
D000818:Animals; D001483:Base Sequence; D002490:Central Nervous System / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D055786:Gene Knockout Techniques; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D055495:Neurogenesis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D012727:Sex Characteristics; D012726:Sexual Behavior, Animal / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics*
D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; C103226:fru protein, Drosophila