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

Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system.
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DOI:
10.1016/j.cub.2013.11.035
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发表时间:
2014-02-03
期刊:
影响因子:
9.2
通讯作者:
Goodwin, Stephen F.
Goodwin, Stephen F.
中科院分区:
生物学1区
文献类型:
--
作者:
Neville, Megan C.;Nojima, Tetsuya;Ashley, Elizabeth;Parker, Darren J.;Walker, John;Southall, Tony;Van de Sande, Bram;Marques, Ana C.;Fischer, Bettina;Brand, Andrea H.;Russell, Steven;Ritchie, Michael G.;Aerts, Stein;Goodwin, Stephen F.

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在果蝇中,雄性求偶行为很大程度上是由fruitless(fru)基因调控的。fru编码一组推定的转录因子,其通过控制性二态神经元回路的发育来促进男性性行为。关于Fru蛋白在转录调控水平上的功能或同种型多样性在男性特异性神经系统形成中的作用知之甚少。为了表征性别特异性Fru亚型在指定男性行为中的作用,我们产生了新的亚型特异性突变体,并使用基因组方法来识别发育过程中的直接Fru亚型靶点。我们证明,所有的Fru亚型直接靶向参与神经系统发育的基因,个别亚型表现出独特的结合特异性。我们观察到fru的行为表型是由单一亚型或亚型的组合来指定的。最后,我们说明了这些数据的实用性,用于识别新的性二态基因组增强子和新的下游调节男性性行为。这些发现表明,Fru亚型多样性促进了基因表达的冗余性和特异性,并且神经元发育基因的调节可能是fru在男性特异性神经系统特化中最古老和保守的作用。同种型特异性fru突变体揭示了功能冗余和特异性Fru同种型特异性基因组占有的特点是在果蝇神经系统中所有的Fru同种型直接靶向神经元形态发生基因同种型特异性基序与特定的Fru同种型占有相关Neville et al.通过产生新的同种型特异性突变体,沿着使用基因组方法鉴定发育过程中直接的Fruitless同种型靶标,来表征性别特异性Fruitless同种型在果蝇中指定雄性行为中的作用。
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. 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. 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. Isoform-specific fru mutants reveal both functional redundancy and specificity Fru isoform-specific genomic occupancy is characterized in the Drosophila nervous system All Fru isoforms directly target neuronal morphogenesis genes Isoform-specific motifs are associated with specific Fru isoform occupancy Neville et al. characterize the roles of sex-specific Fruitless isoforms in specifying male behavior in Drosophila by generating novel isoform-specific mutants, along with using a genomic approach to identify direct Fruitless isoform targets during development.
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