Direct targets of the<i>D. melanogaster</i>DSXF protein and the evolution of sexual development

Luo, Shengzhan D.; Shi, Guang; Baker, Bruce S.

doi:10.1242/dev.065227

Cited by 71 publications

(86 citation statements)

References 49 publications

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“…We attempted to address this question, as described below. Previous work identified regions of likely Dsx DNAbinding activity and a consensus 13-bp Dsx binding motif (GCAACAATGTTGC) (5,13,32). The Lgr3 locus contains three potential Dsx binding sites: a 9/13-bp partial binding site match in R17G11 (GagACAATGTgaC, with mismatches in lowercase), and two 10-and 11-bp partial matching sites in R17H01 (GCAACAtTGaaGt and GttACAtTGTTGC).…”

Section: Resultsmentioning

confidence: 99%

“…The Lgr3 locus contains three potential Dsx binding sites: a 9/13-bp partial binding site match in R17G11 (GagACAATGTgaC, with mismatches in lowercase), and two 10-and 11-bp partial matching sites in R17H01 (GCAACAtTGaaGt and GttACAtTGTTGC). We focused on R17H01 because of its closer matches to the 13-bp motif identified previously (5). We mutated these putative binding sites to disrupt Dsx binding, and hence suggest whether Dsx directly regulates R17H01 expression.…”

Section: Resultsmentioning

confidence: 99%

“…Several direct Dsx targets and a well-conserved 13-bp Dsx binding site have been identified (5)(6)(7)(8)(9)(10)(11)(12)(13). Many Dsx target genes encode well-known transcription factors and cell-cell signaling molecules that function sex-nonspecifically in most tissues in which they are expressed.…”

mentioning

confidence: 99%

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Sex-specific regulation of Lgr3 in Drosophila neurons

Meissner

Luo

Dias

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The development of sexually dimorphic morphology and the potential for sexually dimorphic behavior in Drosophila are regulated by the Fruitless (Fru) and Doublesex (Dsx) transcription factors. Several direct targets of Dsx have been identified, but direct Fru targets have not been definitively identified. We show that Drosophila leucine-rich repeat G protein-coupled receptor 3 (Lgr3) is regulated by Fru and Dsx in separate populations of neurons. Lgr3 is a member of the relaxin-receptor family and a receptor for Dilp8, necessary for control of organ growth. Lgr3 expression in the anterior central brain of males is inhibited by the B isoform of Fru, whose DNA binding domain interacts with a short region of an Lgr3 intron. Fru A and C isoform mutants had no observed effect on Lgr3 expression. The female form of Dsx (Dsx F ) separately up-and down-regulates Lgr3 expression in distinct neurons in the abdominal ganglion through female-and male-specific Lgr3 enhancers. Excitation of neural activity in the Dsx F -up-regulated abdominal ganglion neurons inhibits female receptivity, indicating the importance of these neurons for sexual behavior. Coordinated regulation of Lgr3 by Fru and Dsx marks a point of convergence of the two branches of the sex-determination hierarchy.M ost animal species are comprised of female and male individuals, in which sex differences in form and behavior are specified by their genetic makeup. The developmental processes by which genes build sex-specific differences into the nervous system, and hence encode the potential for sex-specific behavior, have long been of interest (1).In Drosophila melanogaster the assessment of the number of X chromosomes leads to sex-differential splicing of transcripts from genes making up the sex-determination hierarchy, in particular the terminal genes of that hierarchy, fruitless (fru) and doublesex [dsx (2), reviewed in ref. 3]. fru and dsx encode sexspecific Zn-finger transcription factors that alter, either directly or indirectly, the expression of downstream genes to produce the sexually dimorphic elements of flies. The male-specific forms of Fru (Fru M ) act in a subset of the neurons within the male's nervous system to establish the potential for social interactions such as courtship behavior and aggression (reviewed in ref.3). In contrast, Dsx acts in subsets of both neural and nonneural tissues of males and females to regulate behavioral and nonbehavioral aspects of sexual development (reviewed in ref.3).Although the mechanisms regulating the production of the sexspecific isoforms of the Fru and Dsx proteins are well-established (4), how these proteins in turn function is only beginning to be elucidated. Several direct Dsx targets and a well-conserved 13-bp Dsx binding site have been identified (5-13). Many Dsx target genes encode well-known transcription factors and cell-cell signaling molecules that function sex-nonspecifically in most tissues in which they are expressed. However, in other tissues, Dsx directs the sexspecific expression of these gene...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Sex-specific regulation of Lgr3 in Drosophila neurons

Meissner

Luo

Dias

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…We previously found that the Fmo-2 gene of all five sequenced species in the melanogaster subgroup contained a sequence matching at least 12 bp of the 13-bp optimal DSX-binding site (24). To test whether the conservation of the DSX-binding site at the Fmo-2 gene correlates with conservation of sexually dimorphic Fmo-2 expression, we examined the Fmo-2 expression in six species from the melanogaster subgroup, as well as three species in the melanogaster group but not in the melanogaster subgroup (Fig.…”

Section: Fmo-2 Transcription Is Directly Regulated By Dsx Through Anmentioning

confidence: 99%

“…To fulfill this need, we previously identified potential direct dsx target genes through a genome-wide screen for DSX binding sites (24). Characterization of these candidate genes should facilitate our understanding of the molecular mechanisms and evolution of the differences between males and females.…”

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Constraints on the evolution of a doublesex target gene arising from doublesex’s pleiotropic deployment

Luo

Baker

2015

Proc. Natl. Acad. Sci. U.S.A.

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"Regulatory evolution," that is, changes in a gene's expression pattern through changes at its regulatory sequence, rather than changes at the coding sequence of the gene or changes of the upstream transcription factors, has been increasingly recognized as a pervasive evolution mechanism. Many somatic sexually dimorphic features of Drosophila melanogaster are the results of gene expression regulated by the doublesex (dsx) gene, which encodes sex-specific transcription factors (DSX F in females and DSX M in males). Rapid changes in such sexually dimorphic features are likely a result of changes at the regulatory sequence of the target genes. We focused on the Flavin-containing monooxygenase-2 (Fmo-2) gene, a likely direct dsx target, to elucidate how sexually dimorphic expression and its evolution are brought about. We found that dsx is deployed to regulate the Fmo-2 transcription both in the midgut and in fat body cells of the spermatheca (a female-specific tissue), through a canonical DSX-binding site in the Fmo-2 regulatory sequence. In the melanogaster group, Fmo-2 transcription in the midgut has evolved rapidly, in contrast to the conserved spermathecal transcription. We identified two cis-regulatory modules (CRM-p and CRM-d) that direct sexually monomorphic or dimorphic Fmo-2 transcription, respectively, in the midguts of these species. Changes of Fmo-2 transcription in the midgut from sexually dimorphic to sexually monomorphic in some species are caused by the loss of CRM-d function, but not the loss of the canonical DSX-binding site. Thus, conferring transcriptional regulation on a CRM level allows the regulation to evolve rapidly in one tissue while evading evolutionary constraints posed by other tissues.sex determination | transcription factors | DNA binding site | evolution H ow sex-specific characteristics are generated during development, what roles they have in the biology of an organism, and how they have evolved are fundamental questions in biology. In Drosophila melanogaster, the molecular mechanisms leading to the sex-specific and temporally and spatially restricted deployment of the transcription factors encoded by the terminal genes in the sex-determination regulatory hierarchy, doublesex (dsx) and fruitless (fru), have been well documented (1-4). In addition, although it has been established that the FRU M and DSX M and DSX F proteins control nearly all aspects of somatic sexual differentiation, including anatomical and behavioral differences, much less is known about the direct target genes through which these transcription factors act (2, 3, 5-11).It has been increasingly recognized that evolutionary significant changes in gene expression are often a result of mutations in the regulatory sequences of genes, rather than in their coding sequences (12). Furthermore, it has been noted that evolutionary changes are most likely in the cis-acting regulatory elements of the downstream targets of transcription factors, rather than in the genes encoding the transcription factors (13,14). This finding...

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The direct regulation of Aalbdsx on AalVgR is indispensable for ovarian development in Aedes albopictus

Jin

Zhao

Liu

et al. 2020

Pest Management Science

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BACKGROUND Aedes albopictus is an important vector with an extensive worldwide distribution. Only female mosquitoes play a significant role in the transmission of pathogens. Doublesex (dsx) is a central nexus gene in the insect somatic sex determination hierarchy. RESULTS In this study, we characterized the full‐length sex‐specific splicing forms of the Ae. albopictus dsx (Aalbdsx) gene. Then, we identified 15 direct target genes of DSX in adult females using digital gene expression combined with quantitative real‐time polymerase chain reaction (qPCR) by performing a chromatin immunoprecipitation (ChIP) assay with specific DSX antibodies. Knockdown of Aalbdsx suppressed ovarian development and decreased the transcript levels of the Aalbdsx target vitellogenin receptor (VgR) gene, whereas vitellogenin (Vg) expression showed an increase in the fat body. Genes in the major Vg regulatory pathway were also up‐regulated. CONCLUSION Our results suggest that both Vg and VgR are direct target genes of Aalbdsx and that direct regulation of Aalbdsx on VgR is indispensable for ovarian development in Ae. albopictus, which not only provides a reference for the further elucidation of the evolutionarily conserved role of dsx in Ae. albopictus sexual differentiation but also reveals potential molecular targets for application to the development of sterile male mosquitoes to be released for vector control. © 2020 Society of Chemical Industry

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Direct targets of theD. melanogasterDSXF protein and the evolution of sexual development

Cited by 71 publications

References 49 publications

Sex-specific regulation of Lgr3 in Drosophila neurons

Sex-specific regulation of Lgr3 in Drosophila neurons

Constraints on the evolution of a doublesex target gene arising from doublesex’s pleiotropic deployment

The direct regulation of Aalbdsx on AalVgR is indispensable for ovarian development in Aedes albopictus

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