Sex- and Tissue-Specific Functions of Drosophila Doublesex Transcription Factor Target Genes

Clough, Emily; Jimenez, Elvira; Kim, Yoo-Ah; Whitworth, Cale; Neville, Megan C; Hempel, Leonie U.; Pavlou, Hania J.; Chen, Zhenxia; Sturgill, David; Dale, Ryan K.; Smith, Harold E.; Przytycka, Teresa M.; Goodwin, Stephen F.; Doren, Mark Van; Oliver, Brian

doi:10.1016/j.devcel.2014.11.021

Cited by 134 publications

(184 citation statements)

References 79 publications

(99 reference statements)

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“…Of these, isoforms A, B, and C have detectable nervous system expression and are candidates for regulators of Lgr3 expression in the male nervous system (31). We examined the expression of R19B09.3A in flies individually mutant for the A, B, or C isoforms (13,28), and found that R19B09.3A expression was only affected by the absence of Fru B (Fig. 3 A and B).…”

Section: Resultsmentioning

confidence: 99%

“…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%

“…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.…”

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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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“…In female somatic cells, Sxl controls the alternative splicing of transformer (tra), which together with transformer2 (tra2) controls the alternative splicing of doublesex (dsx) and fruitless (fru). dsx and fru in turn encode sex-specific transcription factors that control male versus female morphology, physiology, and behavior (3,4). In addition, Sxl represses the male-specific dosage compensation system by regulating male-specific lethal 2 (msl-2) both at the level of alternative splicing and translational control (5).…”

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confidence: 99%

spenito is required for sex determination in Drosophila melanogaster

Dong

Perrimon

2015

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

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Sex-lethal (Sxl) encodes the master regulator of the sex determination pathway in Drosophila and acts by controlling sex identity in both soma and germ line. In females Sxl maintains its own expression by controlling the alternative splicing of its own mRNA. Here, we identify a novel sex determination gene, spenito (nito) that encodes a SPEN family protein. Loss of nito activity results in stem cell tumors in the female germ line as well as female-to-male somatic transformations. We show that Nito is a ubiquitous nuclear protein that controls the alternative splicing of the Sxl mRNA by interacting with Sxl protein and pre-mRNA, suggesting that it is directly involved in Sxl auto-regulation. Given that SPEN family proteins are frequently mutated in cancers, our results suggest that these factors might be implicated in tumorigenesis through splicing regulation.germ-line stem cell | sex determination | alternative splicing S ex determination in Drosophila is under the control of the master regulatory gene Sex-lethal (Sxl) (1). Sxl acts downstream of the X-chromosome counting mechanism and encodes a female-specific RNA binding protein. Once activated, Sxl maintains its own expression by regulating the alternative splicing of its pre-mRNA. Sxl controls female fate by controlling somatic and germ-line sex identity as well as dosage compensation (2). In female somatic cells, Sxl controls the alternative splicing of transformer (tra), which together with transformer2 (tra2) controls the alternative splicing of doublesex (dsx) and fruitless (fru). dsx and fru in turn encode sex-specific transcription factors that control male versus female morphology, physiology, and behavior (3, 4). In addition, Sxl represses the male-specific dosage compensation system by regulating male-specific lethal 2 (msl-2) both at the level of alternative splicing and translational control (5

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“…[91][92][93][94][95][96] Both the isoforms of dsx act antagonistically on different targets present on multiple tissues with one being a positive regulator of certain gene in one tissue while negative regulator in others and vice versa. 97 Several other genes also play a role in the development of sex comb, for example, wg, dpp, Distal-less (DII), dachshund (dac), rotund (rn), and bric-a-brac (bab) ( Table 1). 97,98 Various types of pigmentation variations within and between closely related species are observed in many insect taxa as well as in Drosophila spp.…”

Section: Genetic Basis For Sexual Dimorphismmentioning

confidence: 99%

The genetics of sexual behavior in Drosophila

Singh¹,

Singh²

2016

AGG

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Genes play a profound role in the regulation of Drosophila behavioral system, either sexual or nonsexual. Those regulating sexual behavior may lead to differences at the level of species, thus causing behavioral isolation. Courtship in Drosophila involves several behavioral repertoires which are controlled genetically. It involves the use of several sensory stimuli that may affect the behavioral responses of both the sexes. These sensory signals are sex specific, and the specificity is due to differential expression of the genes. In addition to the premating behavior, certain candidate genes also affect several postmating responses. Genes also play a magnificent role in the differentiation of two morphologically and behaviorally distinct sexes as well as in their brain structures, which may explain the basis of sexual dimorphism in Drosophila. Also, the advancement in the area of system genetics like the use of mutants and GAL4/ UAS and CRISPR/Cas9 systems provides a much better way to understand the role of genes in controlling several aspects of behavior more closely.

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Sex- and Tissue-Specific Functions of Drosophila Doublesex Transcription Factor Target Genes

Cited by 134 publications

References 79 publications

Sex-specific regulation of Lgr3 in Drosophila neurons

Sex-specific regulation of Lgr3 in Drosophila neurons

spenito is required for sex determination in Drosophila melanogaster

The genetics of sexual behavior in Drosophila

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