An extracellular activator of the Drosophila JAK/STAT pathway is a sex-determination signal element

Sefton, Louise; Timmer, John R.; Zhang, Yan; Béranger, Florence; Cline, Thomas W.

doi:10.1038/35016119

Cited by 69 publications

(67 citation statements)

References 16 publications

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“…Females tend to have a greater immune response to a variety of stimuli, including immunization, infection, and autoantigens (39). JAK1 is an essential component of IFN signaling pathway, and, in Drosophila, the homologous JAK-STAT pathway has been implicated in the additional role of sex determination and sexual identity (40). The gender differences that we describe in gene expression in placenta suggest some interesting candidates for the pathways that might be responsible for gender differences observed in fetal development and physiology.…”

Section: Genes That Define Interindividual Variation In Villus Sectiomentioning

confidence: 99%

Gene expression patterns in human placenta

Sood¹,

Zehnder²,

Druzin

et al. 2006

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

391

289

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The placenta is the principal metabolic, respiratory, excretory, and endocrine organ for the first 9 months of fetal life. Its role in fetal and maternal physiology is remarkably diverse. Because of the central role that the placenta has in fetal and maternal physiology and development, the possibility that variation in placental gene expression patterns might be linked to important abnormalities in maternal or fetal health, or even variations in later life, warrants investigation. As an initial step, we used DNA microarrays to analyze gene expression patterns in 72 samples of amnion, chorion, umbilical cord, and sections of villus parenchyma from 19 human placentas from successful full-term pregnancies. The umbilical cord, chorion, amnion, and villus parenchyma samples were readily distinguished by differences in their global gene-expression patterns, many of which seemed to be related to physiology and histology. Differentially expressed genes have roles that include placental trophoblast secretion, signal transduction, metabolism, immune regulation, cell adhesion, and structure. We found interindividual differences in expression patterns in villus parenchyma and systematic differences between the maternal, fetal, and intermediate layers. A group of genes that was expressed in both the maternal and fetal villus parenchyma sections of placenta included genes that may be associated with preeclampsia. We identified sets of genes whose expression in placenta was significantly correlated with the sex of the fetus. This study provides a rich and diverse picture of the molecular variation in the placenta from healthy pregnancies.microarray ͉ pregnancy ͉ transcriptome ͉ preeclampsia T he placenta is a temporary organ that performs the functions of several adult organs for the growing fetus. The placenta is designed uniquely for exchange of oxygen, nutrients, antibodies, hormones, and waste products between the mother and fetus and may carry valuable information about the pregnancy. Although a placenta after delivery is among the most easily accessible human tissues, it is usually discarded after a cursory evaluation (1). Several pregnancy disorders including preeclampsia (PE) and preterm labor are associated with placental pathology. Also, epidemiologic studies suggest that there are ''fetal origins'' that predispose adults to cardiovascular, metabolic, and endocrine diseases (2). Also, low-birth-weight fetuses associated with large placentas are associated with increased neonatal morbidity indicating abnormal placental activity in such scenarios (3, 4). The investigation of placenta may provide valuable insights into placental functions and help identify molecular mechanisms that have both immediate and long lasting effects on health of the fetus.A schematic representation of the placenta is given in Fig. 1, with both the placental disk proper and the reflected membranes. The placenta is a composite organ of trophectoderm-derived cells and cells that are derived from the inner cell mass (ICM)͞epiblast, and a minor co...

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Section: Genes That Define Interindividual Variation In Villus Sectiomentioning

confidence: 99%

Gene expression patterns in human placenta

Sood¹,

Zehnder²,

Druzin

et al. 2006

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

391

289

View full text Add to dashboard Cite

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“…In flies, a set of feminizing genes on X called X signal elements (XSEs) communicates X-chromosome number (Cline 1988;Cline 1991, 1993;Sefton et al 2000;Salz and Erickson 2010), but ploidy appears not to be signaled by a corresponding set of masculinizing autosomal genes (Erickson and Quintero 2007). Only a single autosomal signal element (ASE) has been identified through extensive genetic screens (Barbash and Cline 1995).…”

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confidence: 99%

“…In the fruit fly, the target of the X:A signal is Sxl (sex-lethal), a sex-determining switch gene that induces female development when active and male development when inactive (Cline and Meyer 1996). A set of feminizing XSEs communicates X-chromosome number (Cline 1988;Cline 1991, 1993;Sefton et al 2000) by activating Sxl transcription in a dose-dependent manner. The double dose of XSEs in 2X:2A embryos turns Sxl on, while the single dose in 1X:2A embryos does not.…”

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confidence: 99%

Molecular antagonism between X-chromosome and autosome signals determines nematode sex

et al. 2013

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Sex is determined in Caenorhabditis elegans by the ratio of X chromosomes to the sets of autosomes, the X:A signal. A set of genes called X signal elements (XSEs) communicates X-chromosome dose by repressing the masculinizing sex determination switch gene xol-1 (XO lethal) in a dose-dependent manner. xol-1 is active in 1X:2A embryos (males) but repressed in 2X:2A embryos (hermaphrodites). Here we showed that the autosome dose is communicated by a set of autosomal signal elements (ASEs) that act in a cumulative, dose-dependent manner to counter XSEs by stimulating xol-1 transcription. We identified new ASEs and explored the biochemical basis by which ASEs antagonize XSEs to determine sex. Multiple antagonistic molecular interactions carried out on a single promoter explain how different X:A values elicit different sexual fates. XSEs (nuclear receptors and homeodomain proteins) and ASEs (T-box and zinc finger proteins) bind directly to several sites on xol-1 to counteract each other's activities and thereby regulate xol-1 transcription. Disrupting ASE-and XSE-binding sites in vivo recapitulated the misregulation of xol-1 transcription caused by disrupting cognate signal element genes. XSE-and ASE-binding sites are distinct and nonoverlapping, suggesting that direct competition for xol-1 binding is not how XSEs counter ASEs. Instead, XSEs likely antagonize ASEs by recruiting cofactors with reciprocal activities that induce opposite transcriptional states. Most ASE-and XSE-binding sites overlap xol-1's -1 nucleosome, which carries activating chromatin marks only when xol-1 is turned on. Coactivators and corepressors tethered by proteins similar to ASEs and XSEs are known to deposit and remove such marks. The concept of a sex signal comprising competing XSEs and ASEs arose as a theory for fruit flies a century ago. Ironically, while the recent work of others showed that the fly sex signal does not fit this simple paradigm, our work shows that the worm signal does.

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“…In contrast, in female embryos two X chromosomes provide sufficient amounts of positively acting factors that sxl expression is induced. One of these positively acting factors is upd, and mutations in upd (called sisC) have reduced sxl expression (25). Further experiments have indicated that the JAK/STAT pathway regulates sxl expression, however the mechanism of this regulation is not understood (25,26).…”

Section: Sex Determinationmentioning

confidence: 99%

“…Similarly, os flies have small eyes with fewer ommatidia but, unlike hop mutants, do not have irregular ommatidial arrays or duplicated bristles (57). The molecular lesion that causes this phenotype is not definitively known, but it is likely to be in the regulatory region of the upd locus because os is a viable mutation and a null allele of upd (yc43) is embryonic lethal (3,4,25). The small-eye phenotype in os flies can be fully rescued by ectopic misexpression of upd (57).…”

Section: Eye Developmentmentioning

confidence: 99%