Dmdsx
novel zinc finger transcription factor - regulates sexual differentiation of both sexes - controls somatic sexual identity - regulates the connectivity of a neural circuit controlling Drosophila male courtship song
Please see the JBrowse view of Dmel\dsx for information on other features
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AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.
Stop-codon suppression (UAG) postulated; FBrf0216884.
Gene model reviewed during 5.44
Gene model reviewed during 5.49
Gene model reviewed during 6.50
549, 427 (aa); 57.4, 44.8 (kD predicted)
amino-terminal end
female-specific carboxy-terminal end
male-specific carboxy-terminal end
female-specific
male-specific
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\dsx using the Feature Mapper tool.
The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).
Comment: male
Comment: maternally deposited
Comment: male-specific transcript only
dsx shows greater expression in male than female anterior Malpighian tubules.
A probe directed against the male-specific dsx exon shows expression in wandering third instar larval and white prepupal leg discs. Transcripts are present in males in the presumptive first tarsal segment but not in T2 or T3 discs or in the female T1. At 24hr APF, dsx transcripts in the male T1 leg are confined to the presumptive sex comb region.
The male-specific form of dsx transcript is expressed solely in male embryos. It is expressed in male-specific somatic gonadal precursor cells.
dsx transcript is expressed in the larval and adult CNS. RT-PCR analysis using transcript-isoform-specific primers shows male- and female-specific expression.
Comment: referred to as dsx-pC1
Comment: referred to as dsx-pC2
Comment: referred to as P1. Antibody detects male-specific protein.
In male larvae: From 36-40 h, the male-specific isoform of dsx is present in a crescent within T1 of the prothoracic leg disc, and there is no overlap with ac. At 44 h, dsx signal increases across the epithelium of tarsal segments distal to T1 (i.e. toward disc center) and is present in some clusters of ac-positive cells. (D) At 48 h, dsx is present in swaths of epithelial cells in T1-T4 and overlaps in these segments with subsets of the ac-positive cells that are proneural clusters.
In male pupae: At 0h APF, dsx is present across the T2-T4 tarsal segment epithelium in male prothoracic leg discs as well as in subsets of cells expressing ase in T4 and T5. At 6h APF, dsx is present in the tarsal segment epithelium of prothoracic leg discs at 6 h APF. DSX overlaps with neur expression in several cells across T1-T5, and in a transverse row of cells in T1 that likely correspond to the sex comb bristle lineages.
dsx expression is first apparent in both male and female wandering third instar larval T1 leg discs in an anterior-ventral crescent that overlaps the distal but not the proximal part of the Scr expression domain in the distal tibia and first tarsal segment region of the disc. In some males, the dsx expression extends more distally and posteriorly. No dsx expression is observed in the T2 or T3 leg discs. In prepupal legs at 5hr APF, dsx expression is clearly seen in the ventral-anterior side of the distal first tarsal segment in both male and female T1 legs. The overlap with Scr expression, which extends more proximally, is more extensive in males than females. In males but not females, dsx expression is also seen in small dorsal and ventral patches in the more distal tarsal segments. dsx expression is thus sexually dimorphic from the prepupal stage in the leg discs. At 16hr APF, when the sex comb begins its rotation, dsx expression in the distal first tarsal segment is clearly dimorphic. In males, it is expressed strongly around the presumptive sex comb, while expression in the female is lower. Male expression in the other tarsal segments has disappeared by this time. By 24hr APF, when sex comb rotation is complete, dsx and Scr develop roughly complementary expression patterns in the male leg. dsx is highest in the sex comb teeth and surrounding epidermal cells, while Scr expression is low or absent in sex comb teeth but highest in adjacent epidermal cells. The pattern is maintained at later stages. In females, dsx expression becomes very low or undetectable, and Scr expression in the distal first tarsal segment is much lower than in males.
Antibodies to the male-specific form of dsx detect protein in all male-specific somatic gonadal precursor cells in late embryo but not in the germline cells. These somatic cells are intermingled with germline cells. Male-specific dsx is expressed in all posterior somatic gonadal cells expressing eya and either Sox100B or tj. There is another population of cells that wraps around the embryonic testis at embryonic stage 17 that express Sox100B but not dsx. dsx is also detected in hub cells in stage 17 embryos. The male-specific dsx isoform is detected in cyst cells in larval and adult testis.
In the late third instar larval central nervous system, dsx protein is distributed in a relatively small number of cells in the brain lobes and ventral nerve cord. The most broad and intense dsx immunoreactivity in the CNS is observed in pupae 1-2 days APF. Labeled cells in each brain hemisphere include 2 anterior-dorsal neurons in the superior protocerebrum, 2-3 lateral subesophageal neurons, 1 neuron located medially in the ventral-most part of the subesophageal ganglion, and two groups of 30-50 cells each located posteriorly and dorsally to the mushroom body calyx; about 20-30 cells of these last two groups are non-neuronal. In the ventral nerve cord, labeled cells include 18-24 neurons per side in the prothoracic and metathoracic ganglia; another 38-42 neurons in the thoracic ganglia; and 200-300 neurons in the abdominal ganglia. A similar but fainter pattern is observed in later pharate adults (3-4 days APF), and most dsx-expressing cells observed in pupal CNS are also observed in the adult CNS, with much fainter immunoreactivity in female adults than in male adults.
Comment: A FLP/FRT strategy shows P{GMR71G01-lexA} drives expression in adult ingestion neuron 1 when combined with TI{GAL4::p65}CCKLR-17D3GAL4::p65.
Comment: when combined with Mi{Trojan-p65AD.2}Gad1MI09277-Tp65AD.2
Comment: when combined with P{dVP16AD}VGlutOK371-dVP16AD
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with Mi{Trojan-p65AD.2}Gad1MI09277-Tp65AD.2
Comment: when combined with Mi{Trojan-p65AD.2}Gad1MI09277-Tp65AD.2
Comment: when combined with Mi{Trojan-p65AD.2}Gad1MI09277-Tp65AD.2
when combined with P{elav-VP16.AD}
Comment: when combined with P{dVP16AD}VGlutOK371-dVP16AD
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with P{elav-VP16.AD}
Comment: when combined with P{dVP16AD}VGlutOK371-dVP16AD
when combined with P{elav-VP16.AD}
Comment: when combined with P{dVP16AD}VGlutOK371-dVP16AD
Comment: when combined with P{elav-GAL4.AD}
Comment: when combined with P{Trh-p65.AD}
Comment: when combined with P{R41A01-p65.AD} (combination referred to as 'dsx ∩ R41A01')
Comment: when combined with P{R41A01-p65.AD} (combination referred to as 'dsx ∩ R41A01')
Comment: crescent pattern
Comment: base
Comment: nonneuronal
Comment: pericuticular
Comment: pericuticular
Comment: pericuticular
Comment: 24h APF
Comment: 24h APF
Comment: 24h APF
Comment: 48h APF
Comment: 48h APF
Comment: 96h APF
Comment: 96h APF
Comment: referred to as pC1
Comment: referred to as pC2
Comment: A FLP/FRT strategy shows TI{lexA::p65}dsxlexA::p65 drives expression in adult ingestion neuron 1 when combined with TI{GAL4::p65}CCKLR-17D3GAL4::p65.
JBrowse - Visual display of RNA-Seq signals
View Dmel\dsx in JBrowsePlease Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
polyclonal
monoclonal
dsx is necessary for the differentiation of both male and female specific adult cuticular structures.
"DsxF" protein prevents the induction of dpp by hh in the repressed male primordium of female genital discs, whereas "DsxM" protein blocks the wg pathway in the repressed female primordium of male genital discs. "DsxF" protein is continuously required during female development to prevent activation of dpp in the repressed male primordium and during pupation for female genital cytodifferentiation. In males, "DsxM" is not continuously required during larval development to block the wg signaling pathway in the female genital primordium, and it does not appear to be needed during pupation for male genital cytodifferentiation.
Ectopic somatic expression of the female product of tra is sufficient to feminise XY germ cells. This feminisation depends upon the tra2 gene, but does not seem to require a functional dsx gene. However, feminisation of XY germ cells by the female product of tra can be blocked by the male form of dsx protein.
dsx is capable of repressing Dgri\Yp1 and Dgri\Yp2 in D.melanogaster males.
The female dsx protein plays an important role in sexual behaviour.
DNA binding properties of purified protein dimers to dsxA, a specific DNA regulation site, is investigated; protein binding to dsxA is indistinguishable.
The dsx splicing enhancer contains A/C-rich splicing enhancer (ACE) motifs. A single copy of the repeat element strongly enhances splicing of vertebrate splice sites in vertebrate cells.
Two oligomerisation domains in male- and female-specific dsx are identified by yeast two-hybrid interaction assays and in vitro physical studies. Each protein has two oligomerisation domains; one sex independent, the other sex specific. The common function of the two domains is to oligomerize the full length protein and their specialised function is to form a dimeric DNA binding unit and a sex-specific transcriptional activation or repression unit.
The physical characteristics of the dsx proteins have been studied using mobility shift assays.
The preferred target site for dsx binding has been determined using affinity selection of random oligonucleotides and found to be a sequence with dyad symmetry, suggesting that dsx binds to its target sequence in a dimeric form. Two independent dimerization domains in the amino terminal and carboxy terminal regions of female and male specific dsx proteins have been identified and mapped using the yeast two-hybrid technique. dsx proteins expressed in the fly exist in a multimeric form.
Sequences of the dsx and Dvir\dsx splicing enhancers are highly divergent except for the presence of nearly identical 13 nucleotide repeat elements (that are predominantly single stranded) and a stretch of nucleotides at the 5' and 3' ends of the enhancers. Organisation of sequences within the splicing enhancers results in a structure in which each of the repeat elements is single stranded and therefore accessible for specific recognition by the RNA binding domain of tra2.
Both HeLa and Kc cell nuclear extracts have been used for UV cross-linking experiments to determine which proteins bind to dsxRE as part of the native tra- and tra2-dependent dsx enhancer complex (dsxEC). Rbp1 and SRp30 have been identified that bind the 13-nucleotide repeats and purine rich element (PRE), respectively, of the dsx repeat element (dsxRE).
dsx mutant males are reproductively abnormal. The abnormality may stem from sexual differentiation defects in CNS, PNS or both.
Site directed mutagenesis, protein binding and germline transformation experiments identify and characterise the activity of a simple mini-enhancer from the fat body enhancer (FBE region) consisting of a single binding site (dsxA) for the dsx protein and two others for other regulatory proteins (slbo and ref1). One copy of this enhancer is sufficient to direct the sex and fat body specificities of Yp1 transcription.
Fragments of normally cis-spliced ftz pre-mRNA substrates are trans spliced in mammalian nuclear extracts. Trans splicing is promoted by a constitutively active splicing enhancer located downstream of a 3' splice site. SR proteins also promote the functional interaction of 5' and 3' splice sites in trans.
The RNA target sequences recognised by Rbp1 have been determined using the in vitro selection approach and were found within the repeat region and in the purine rich region polypyrimidine tract of the regulated female specific 3' splice site of dsx. The Rbp1 protein can activate female specific splicing of dsx in vivo by recognising target sequences present within the pre-mRNA.
Regulated alternative splicing of dsx pre-mRNA requires the dsxRE splicing enhancer, dsx repeat element. The activity of dsxRE requires tra and tra2 and one or more general splicing factors. A purine rich enhancer (PRE) sequence within the RE has been identified, this element functionally synergises with the dsxRE and is required for specific binding of tra2 to the dsxRE. Results demonstrate that positive control of dsx pre-mRNA splicing requires tra- and tra2- dependent assembly of a multiprotein complex on at least two distinct enhancer elements. The dsx repeats R1-5 and the PRE are distinct constitutive splicing enhancer elements.
dsx function is required to direct the development of the genital muscles acting in wild type to repress the development of muscles of the inappropriate sex.
Transcript levels from the dsx gene are not affected by nutrition.
dsx does not appear to materially regulate male sexual behaviour.
In vitro mutagenesis of dsx binding sites demonstrates that in males the dsx gene product acts to directly repress transcription of the yolk genes and in females the dsx gene product activates transcription by acting at the same sites in the fat body enhancer (FBE) driving expression of Ecol\lacZ. Through the male and female dsx proteins the sexual differentiation pathway is connected to a target gene by acting directly, but with opposite effects, on the gene.
Both the male-specific and female-specific dsx proteins share and depend upon the same DNA binding domain for function in vivo, suggesting that both proteins bind to, but differentially regulate, a common set of genes in both sexes.
Female specific splicing of dsx is regulated by tra and tra2, which recruit general, serine/arginine-rich splicing factors to a regulatory element located downstream of a female-specific 3' splice site.
The M2 exon sequence of mouse IgM can stimulate the splicing of the dsx female specific intron, splicing of this intron does not usually occur due to a suboptimal pyrimidine stretch within the 3' splice site.
Transfection analysis in Kc cells with dsx minigene constructs identified 6 copies of a 13 nucleotide sequence in the female-specific fourth exon, that act as cis elements for female-specific splicing of dsx pre-mRNA. UV crosslinking identified tra and tra2 gene products binding to these 13 nucleotide seuqences.
The choice of the sexual pathway taken by sex specific neuroblasts depends on the expression of dsx.
dsx is a known sex determining gene, dsx does not direct the development of sexually dimorphic skeletal muscles.
The male and female products of dsx when expressed in E.coli bind specifically to the fat body enhancer (FBE) of Yp1 and Yp2. This demonstrates a direct interaction between the sex determination hierarchy and a target gene.
tra2 produced in E.coli binds specifically to a site within the female specific exon of dsx pre-mRNA. This site is required for female specific splicing and female specific polyadenylation. Results suggest that tra2 is a positive regulator of dsx pre-mRNA processing.
Cotransfection analyses in which dsx, tra and tra2 cDNAs are expressed in Kc cells revealed that female specific splicing of dsx transcript is positively regulated by tra and tra2 gene products. Analysis of mutant constructs of dsx demonstrates that a portion of the female specific exon is required for regulation of dsx pre-mRNA splicing.
Cotransfection assays to examine regulatory interactions between specific cis-acting sequence elements of dsx pre-mRNA, and tra and tra2 gene products establish that tra and tra2 function to activate the use of the female specific exon.
The tra2 gene product may function to control sexual differentiation by directly regulating the processing of the dsx pre-mRNA.
The mechanism of sex determination in the germ line has been analysed.
Mutant individuals are female and male intersexuals.
The dsx gene regulates sexual differentiation of somatic tissues. Null alleles convert chromosomally male and female flies into sterile intersexes of similar phenotype. Dominant alleles (e.g., dsxD, dsxM, dsxT) transform females into intersexes when heterozygous with a normal allele, and into phenotypic males when homozygous or heterozygous with a dsx-null allele or deficiency, but they have no effect in males. Most alleles at dsx affect both sexes; however, some alleles affect only one sex. The recessive allele dsx11 converts males into intersexes and is complemented by dominant dsx alleles and recessive alleles that affect only females (dsx22) (Baker and Ridge, 1980; Nothiger et al., 1987). Double-mutant combinations of dsx null mutations with loss-of-function alleles at tra, tra2 and ix result in a doublesex phenotype (Mukherjee and Hildreth, 1971; Baker and Ridge, 1980; Nothiger et al., 1987). Double-mutant combinations of dsxD/+ with null alleles of tra and tra2 convert females into phenotypic males or with ix into more male-like intersexes (Baker and Ridge, 1980; Nothiger et al., 1987). The dose of dsx alleles can alter the phenotype; triploid female flies dsxD/+/+ are sterile and with a weak external dsx phenotype (Gowen and Fung, 1957; Nothiger et al., 1987); diploid female flies that are dsxD/+, but also carry a dsx+ duplication Tp(3;Y)P92 are sterile but female in appearance (Nothiger et al., 1987). Germline sexual differentiation is not dependent on dsx+ function; only the chromosomal constitution determines the sex of transplanted dsxM/+, dsx1, dsxD/+ and dsxD/dsx1 germ cells (Nothiger, Roost and Schupbach, 1980; Schupbach, 1982). The dsx+ gene does not appear to encode any vital functions (Baker and Ridge, 1980). The normal body size differences between male and female flies is maintained in dsx-null mutants (Hildreth, 1965) and in females heterozygous for dsxD/+, dsxD/dsx1 (Fung and Gowen, 1957; Baker and Ridge, 1980) and dsxM/+ (Nothiger et al., 1987). The sexcomb bristles on the prothoracic basitarsus in both sexes of dsx-null homozygotes (Hildreth, 1965; Mukherjee and Hildreth, 1971; Baker and Ridge, 1980) and female dsxD/dsx1 (Nothiger et al., 1987) are intermediate in number, morphology and position compared with the sexcomb bristles in normal males and the transverse row bristles in normal females. The central sexcomb bristle is retained in dsx-null mutants (Hildreth, 1965). In dsx-null mutants, the pigmentation of the fifth tergite is intermediate between the completely pigmented male and the posteriorly pigmented female tergite, whereas the sixth tergite is darkly pigmented (Hildreth, 1965; Baker and Ridge, 1980). Female flies that are dsxD/+ or dsxM/+ are similar to dsx homozygotes (Fung and Gowen, 1957; Duncan and Kaufman, 1975; Baker and Ridge, 1980; Nothiger et al. 1987). Male dsx flies have a seventh tergite and sternite with bristles (Hildreth, 1965; Baker and Ridge, 1980). Female flies heterozygous for dominant alleles and either dsx1 or dsx deficiencies have the male number of tergites and sternites with the male pattern of pigmentation (Duncan and Kaufman, 1975; Baker and Ridge, 1980; Nothiger, Roost and Schupach, 1980; Nothiger et al., 1987). By clonal analysis, the action of dsx has been shown to be cell autonomous in the differentiation of the sexcombs and pigmentation of the abdominal tergites; dsx+ is required until the end of the larval period for the proper sexual differentiation of the sexcombs and into the pupal period, close to the time of the termination of divisions of the abdominal histoblasts, for proper sexual differentiation of the abdominal histoblasts and for proper sexual differentiation of the abdomen (Baker and Ridge, 1980). Both male and female genitalia are formed in dsx null mutant flies and in female flies heterozygous for dominant alleles (Fung and Gowen, 1957; Hildreth, 1965; Epper, 1981; Nothiger et al., 1987); a second penis differentiates with a reduced aedeagus and parameres within the female vaginal area (Hildreth, 1965). In dsxD/+ females, the development of the female genitalia and second penis are very similar to that of dsx-null flies, whereas in dsxM/+ females the female genitalia are more severely reduced (Gowen and Fung, 1975; Baker and Ridge, 1980; Nothiger, Roost and Schupach, 1980; Epper, 1981; Nothiger et al., 1987). Male genitalia from dsx null flies and females heterozygous for dsx dominant alleles contain all elements except a basal apodeme but other external structures such as the penis and accessory elements are reduc
The ability of the dsx proteins to restore V-ray formation to a Cele\mab-3 mutant is studied. The male specific splice form of dsx can restore V rays, essentially as well as wild type Cele\mab-3 can. The female specific splice form has no effect.
Source for identity of: dsx CG11094