SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development

Hanley, Neil A.; Hagan, Donna Marie; Clement-Jones, Mark; Ball, Steve; Strachan, Tom; Salas-Cortes, L.; McElreavey, Ken; Lindsay, Susan; Robson, SC; Bullen, P; Ostrer, Harry; Wilson, David I.

doi:10.1016/s0925-4773(99)00307-x

Cited by 272 publications

(215 citation statements)

References 14 publications

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“…Although this study reports our findings using PCR subtractive hybridization, we have since confirmed our findings on SOX9 using DNA microarray analysis. We show here that SOX9, which is essential for chondrogenesis (Bell et al, 1997;Bi et al, 1999;Healy et al, 1999;Olney et al, 1999) and male sexual differentiation (Graves, 1998;Hanley et al, 2000;Hawkins, 1995;Koopman, 1999Koopman, , 2001, is induced by RAR pan-agonists and an RARa selective agonist in retinoid-inhibited breast cancer cell lines. RAR-agonists have been reported to have divergent effects on the regulation of SOX9 in other cells.…”

Section: Discussionmentioning

confidence: 79%

RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition

et al. 2002

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Retinoic acid receptors (RARs) are ligand-dependent transcription factors which are members of the steroid/ thyroid hormone receptor gene family. RAR-agonists inhibit the proliferation of many human breast cancer cell lines, particularly those whose growth is stimulated by estradiol (E2) or growth factors. PCR-amplified subtractive hybridization was used to identify candidate retinoidregulated genes that may be involved in growth inhibition. One candidate gene identified was SOX9, a member of the high mobility group (HMG) box gene family of transcription factors. SOX9 gene expression is rapidly stimulated by RAR-agonists in T-47D cells and other retinoidinhibited breast cancer cell lines. In support of this finding, a database search indicates that SOX9 is expressed as an EST in breast tumor cells. SOX9 is known to be expressed in chondrocytes where it regulates the transcription of type II collagen and in testes where it plays a role in male sexual differentiation. RAR pan-agonists and the RARa-selective agonist Am580, but not RXR agonists, stimulate the expression of SOX9 in a wide variety of retinoid-inhibited breast cancer cell lines. RAR-agonists did not stimulate SOX9 in breast cancer cell lines which were not growth inhibited by retinoids. Expression of SOX9 in T-47D cells leads to cycle changes similar to those found with RARagonists while expression of a dominant negative form of SOX9 blocks RA-mediated cell cycle changes, suggesting a role for SOX9 in retinoid-mediated growth inhibition.

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Section: Discussionmentioning

confidence: 79%

RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition

et al. 2002

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“…In humans, WT1 expression first appears at 32 days postovulation (d.p.o. ) in the gonadal ridges of both male and female embryos and then increases at 41 d.p.o., whereas SRY is most strongly expressed at 44 d.p.o., and both genes are expressed later in fetal development (Hanley et al, 1999(Hanley et al, , 2000. Furthermore, mutations in both genes are associated with gonadal dysgenesis in mice and humans as described above.…”

mentioning

confidence: 89%

Transcriptional activity of testis-determining factor SRY is modulated by the Wilms’ tumor 1 gene product, WT1

2003

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The Wilms' tumor 1 (WT1) and sex-determining region of the Y chromosome (SRY) genes are essential for development of the mammalian gonads and mutations in these genes are associated with gonadal dysgenesis in humans. The SRY gene encodes a transcription factor with one high-mobility group (HMG) box as a DNAbinding domain. WT1 encodes a transcription factor that contains four contiguous C 2 H 2 -type zinc-finger motifs as a DNA/RNA binding or protein-protein interaction domain. Here we report that WT1 binds to and acts synergistically with SRY to activate transcription from a promoter containing SRY-binding sites. This interaction is mediated by the WT1 zinc-finger domain and the SRY HMG box. WT1 mutants associated with Denys-Drash syndrome (DDS), which is characterized by Wilms' tumor, pseudohermaphroditism, and nephropathy, fail to interact with SRY. Wildtype WT1 is recruited to SRYbinding sites in an SRY-dependent manner, whereas DDS mutants are not recruited as efficiently. These results suggest that WT1 forms a complex with SRY to regulate transcription and that this WT1-SRY interaction is important in testis development.

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“…Thus, Sf1 and WT1 are required for gonadal formation. In testicular differentiation they have a synergistic action on the transcription of Sox9 (an autosomal gene closely related to Sry) and Mis (or Amh, anti-Mülle-rian hormone) that are both expressed in Sertolli cells of seminiferous cords [26,27]. In ovarian differentiation, Dax 1, by interacting with SF1, prevents the synergistic action of SF1 and WT1 and thus acts as a repressor of Sox9 and Mis transcription [28,29].…”

Section: Genes Involved In Gonadal Sex Differentiationmentioning

confidence: 99%

Sex determination: the amphibian models

2004

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-We review and discuss current knowledge about sex determination in amphibians. The astonishing wide variety of mechanisms of genotypic sex determination is presented and discussed in an evolutionary context. We recall the natural occurrence of transitory juvenile hermaphroditism in some species. Our present knowledge of the mechanisms of sex determination in amphibians is compared to that in mammals. The influence of epigenetic factors, and especially temperature is highlighted. In amphibians, the influence of temperature on sexual differentiation, that can prevail over genotypic sex determination, remains poorly considered in publications. We suggest that studies on genetic and epigenetic factors of gonadal sex differentiation in amphibians could provide substantial information on the evolutionary process of sex determination mechanisms in current living vertebrates.sex determination mechanisms / sexual differentiation / hermaphroditism / epigenetic factors

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SRY, SOX9, and DAX1 expression patterns during human sex determination and gonadal development

Cited by 272 publications

References 14 publications

RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition

RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition

Transcriptional activity of testis-determining factor SRY is modulated by the Wilms’ tumor 1 gene product, WT1

Sex determination: the amphibian models

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