TY - JOUR

T1 - Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system

AU - Neville, Megan C

AU - Nojima, Tetsuya

AU - Ashley, Elizabeth

AU - Parker, Darren J

AU - Walker, John

AU - Southall, Tony

AU - Van de Sande, Bram

AU - Marques, Ana C

AU - Fischer, Bettina

AU - Brand, Andrea H

AU - Russell, Steven

AU - Ritchie, Michael G

AU - Aerts, Stein

AU - Goodwin, Stephen F

N1 - Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2014/2/3

Y1 - 2014/2/3

N2 - 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.

AB - 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.

KW - Animals

KW - Base Sequence

KW - Central Nervous System/metabolism

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/genetics

KW - Gene Expression Regulation, Developmental/genetics

KW - Gene Knockout Techniques

KW - Male

KW - Molecular Sequence Data

KW - Nerve Tissue Proteins/genetics

KW - Neurogenesis/genetics

KW - Protein Isoforms/genetics

KW - Sex Characteristics

KW - Sexual Behavior, Animal/physiology

KW - Transcription Factors/genetics

U2 - 10.1016/j.cub.2013.11.035

DO - 10.1016/j.cub.2013.11.035

M3 - Article

C2 - 24440396

VL - 24

SP - 229

EP - 241

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 3

ER -