Analysis of the Doublesex Female Protein in Drosophila Melanogaster: Role on Sexual Differentiation and Behavior and Dependence on Intersex

Overview

Journal Genetics

Publisher Oxford University Press

Specialty Genetics

Date 1999 Aug 3

PMID 10430590

Citations 57

Authors

J A Waterbury

L L Jackson

P Schedl

Affiliations

Soon will be listed here.

Abstract

doublesex (dsx) is unusual among the known sex-determination genes of Drosophila melanogaster in that functional homologs are found in distantly related species. In flies, dsx occupies a position near the bottom of the sex determination hierarchy. It is expressed in male- and female-specific forms and these proteins function as sex-specific transcription factors. In the studies reported here, we have ectopically expressed the female Dsx protein (Dsx(F)) from a constitutive promoter and examined its regulatory activities independent of other upstream factors involved in female sex determination. We show that it functions as a positive regulator of female differentiation and a negative regulator of male differentiation. As predicted by the DNA-binding properties of the Dsx protein, Dsx(F) and Dsx(M) compete with each other for the regulation of target genes. In addition to directing sex-specific differentiation, Dsx(F) plays an important role in sexual behavior. Wild-type males ectopically expressing Dsx(F) are actively courted by other males. This acquisition of feminine sex appeal is likely due to the induction of female pheromones by Dsx(F). More extreme behavioral abnormalities are observed when Dsx(F) is ectopically expressed in dsx(-) XY animals; these animals are not only courted by, but also copulate with, wild-type males. Finally, we provide evidence that intersex is required for the feminizing activities of Dsx(F) and that it is not regulated by the sex-specific splicing cascade.

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References

Meise M, Hilfiker-Kleiner D, Dubendorfer A, Brunner C, Nothiger R, Bopp D . Sex-lethal, the master sex-determining gene in Drosophila, is not sex-specifically regulated in Musca domestica. Development. 1998; 125(8):1487-94. DOI: 10.1242/dev.125.8.1487. View

RAYMOND C, Shamu C, Shen M, Seifert K, Hirsch B, Hodgkin J . Evidence for evolutionary conservation of sex-determining genes. Nature. 1998; 391(6668):691-5. DOI: 10.1038/35618. View

Finley K, Edeen P, Foss M, Gross E, Ghbeish N, Palmer R . Dissatisfaction encodes a tailless-like nuclear receptor expressed in a subset of CNS neurons controlling Drosophila sexual behavior. Neuron. 1999; 21(6):1363-74. DOI: 10.1016/s0896-6273(00)80655-8. View

Hedley M, Maniatis T . Sex-specific splicing and polyadenylation of dsx pre-mRNA requires a sequence that binds specifically to tra-2 protein in vitro. Cell. 1991; 65(4):579-86. DOI: 10.1016/0092-8674(91)90090-l. View

Butterworth F . Lipids of Drosophila: a newly detected lipid in the male. Science. 1969; 163(3873):1356-7. DOI: 10.1126/science.163.3873.1356. View

Cline T . Two closely linked mutations in Drosophila melanogaster that are lethal to opposite sexes and interact with daughterless. Genetics. 1978; 90(4):683-98. PMC: 1213913. DOI: 10.1093/genetics/90.4.683. View

Baker B, Ridge K . Sex and the single cell. I. On the action of major loci affecting sex determination in Drosophila melanogaster. Genetics. 1980; 94(2):383-423. PMC: 1214149. DOI: 10.1093/genetics/94.2.383. View

Bownes M, Nothiger R . Sex determining genes and vitellogenin synthesis in Drosophila melanogaster. Mol Gen Genet. 1981; 182(2):222-8. DOI: 10.1007/BF00269661. View

Hung M, Barnett T, Woolford C, Wensink P . Transcript maps of Drosophila yolk protein genes. J Mol Biol. 1982; 154(4):581-602. DOI: 10.1016/s0022-2836(82)80016-8. View

10.

Jallon J . A few chemical words exchanged by Drosophila during courtship and mating. Behav Genet. 1984; 14(5):441-78. DOI: 10.1007/BF01065444. View

11.

McRobert S, Tompkins L . The effect of transformer, doublesex and intersex mutations on the sexual behavior of Drosophila melanogaster. Genetics. 1985; 111(1):89-96. PMC: 1202601. DOI: 10.1093/genetics/111.1.89. View

12.

Nagoshi R, McKeown M, Burtis K, Belote J, Baker B . The control of alternative splicing at genes regulating sexual differentiation in D. melanogaster. Cell. 1988; 53(2):229-36. DOI: 10.1016/0092-8674(88)90384-4. View

13.

Baker B, Wolfner M . A molecular analysis of doublesex, a bifunctional gene that controls both male and female sexual differentiation in Drosophila melanogaster. Genes Dev. 1988; 2(4):477-89. DOI: 10.1101/gad.2.4.477. View

14.

Cline T . Evidence that sisterless-a and sisterless-b are two of several discrete "numerator elements" of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states. Genetics. 1988; 119(4):829-62. PMC: 1203469. DOI: 10.1093/genetics/119.4.829. View

15.

Pirrotta V . Vectors for P-mediated transformation in Drosophila. Biotechnology. 1988; 10:437-56. DOI: 10.1016/b978-0-409-90042-2.50028-3. View

16.

Burtis K, Baker B . Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell. 1989; 56(6):997-1010. DOI: 10.1016/0092-8674(89)90633-8. View

17.

Baker B . Sex in flies: the splice of life. Nature. 1989; 340(6234):521-4. DOI: 10.1038/340521a0. View

18.

Bellen H, OKane C, Wilson C, Grossniklaus U, Pearson R, Gehring W . P-element-mediated enhancer detection: a versatile method to study development in Drosophila. Genes Dev. 1989; 3(9):1288-300. DOI: 10.1101/gad.3.9.1288. View

19.

Nagoshi R, Baker B . Regulation of sex-specific RNA splicing at the Drosophila doublesex gene: cis-acting mutations in exon sequences alter sex-specific RNA splicing patterns. Genes Dev. 1990; 4(1):89-97. DOI: 10.1101/gad.4.1.89. View

20.

Burtis K, Coschigano K, Baker B, Wensink P . The doublesex proteins of Drosophila melanogaster bind directly to a sex-specific yolk protein gene enhancer. EMBO J. 1991; 10(9):2577-82. PMC: 452955. DOI: 10.1002/j.1460-2075.1991.tb07798.x. View