Mouse <i>Dach1</i> and <i>Dach2</i> are redundantly required for Müllerian duct development

Davis, R. J.; Harding, Mark J.; Moayedi, Yalda; Mardon, Graeme

doi:10.1002/dvg.20385

Cited by 44 publications

(33 citation statements)

References 45 publications

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“…The WD forms normally, however double Dach1/2 mutant mice have severe defects in MD formation and differentiation and reduced MD expression of Lhx1 and Wnt7a . This suggests that DACH proteins act upstream of Lhx1 and Wnt7a and regulate expression, either directly or indirectly, of these and possibly other factors important for MD formation (Davis et al, 2008). …”

Section: Müllerian Duct Formationmentioning

confidence: 99%

Molecular Genetics of Müllerian Duct Formation, Regression and Differentiation

Mullen

Behringer²

2014

Sex Dev

171

184

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The Müllerian duct (MD) forms the female reproductive tract (FRT) consisting of the oviducts, uterus, cervix, and upper vagina. FRT function is vital to fertility, providing the site of fertilization, embryo implantation and fetal development. Developmental defects in the formation and diseases of the FRT, including cancer and endometriosis, are prevalent in humans and can result in infertility and death. Furthermore, because the MDs are initially formed regardless of genotypic sex, mesenchymal to epithelial signaling is required in males to mediate MD regression and prevents the development of MD-derived organs. In males, defects in MD regression result in the retention of FRT organs and have been described in several human syndromes. Although to date not reported in humans, ectopic activation of MD regression signaling components in females can result in aplasia of the FRT. Clearly, MD development is important to human health; however, the molecular mechanisms remain largely undetermined. Molecular genetics studies of human diseases and mouse models have provided new insights into molecular signaling during MD development, regression and differentiation. This review will provide an overview of MD development and important genes and signaling mechanisms involved.

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Section: Müllerian Duct Formationmentioning

confidence: 99%

Molecular Genetics of Müllerian Duct Formation, Regression and Differentiation

Mullen

Behringer²

2014

Sex Dev

171

184

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“…Transcriptional co-factors such as Dach1 and -2 seem to also take place in the molecular cascade of MD formation. Whereas inactivation of each corresponding gene does not appear to affect this pathway, combined knock-out results in drastic defect of Müllerian derivatives, tending to show a functional redundancy of these factors (Davis et al 2008). In addition to the key role of the above homeodomain transcription factors in the early steps of MD formation, some signalling molecules have been shown to be involved in this process.…”

Section: Hoxa10mentioning

confidence: 99%

The developing female genital tract: from genetics to epigenetics

Massé¹,

Watrin²,

Laurent³

et al. 2009

Int. J. Dev. Biol.

118

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The mammalian female reproductive tract develops from the Müllerian ducts which differentiate, in a cranial to caudal direction, into oviducts, uterine horns, cervix and the anterior vagina. The developmental processes taking place during this organogenesis are notably under the control of steroid hormones, such as members of the Wnt and Hox families, which regulate key developmental genes. At later stages, steroid hormones also participate in the development of the female genital tract. Chemical compounds homologous to steroids can thus act as agonists or antagonists in fetuses exposed to them. These so-called endocrine disruptors are nowadays found in increasing amounts in the environment and may therefore have a particular impact on such developing organs. Epidemiological studies have revealed that endocrine disruptors have had drastic effects on female health and fertility during the last decades. Furthermore, these adverse effects might be transmitted to subsequent generations through epigenetic modifications. Given the potential hazard of inherited epigenetic marks altering reproduction and/or human health, such molecular mechanisms must be urgently investigated. This review aims to summarize the cellular and molecular mechanisms involved in female genital tract development, to highlight key genes involved in this process and to present epigenetic mechanisms triggered by endocrine disruptors and their consequences in regard to female reproductive tract development. KEY WORDS: genital tract, Hox, Wnt, genetics, epigenetics Development of the urogenital system Relation between urinary and genital tractsMammalian genital tract development is closely related to the urinary system embryogenesis. This relation is ancient in evolution and phylogenetically well conserved. In simple organisms like annelids, they both consist in metamerized nephritic tubules composed of a ciliated funnel oriented towards the coelomic cavity and connected to a vascularised duct that opens to the exterior. This system is involved in metabolites and mature genital cells excretion. In higher vertebrates, the urogenital apparatus comprises the kidneys, gonads, urinary and reproductive ducts. The urinary tract embryonic formation is the result of a three steps process that gives rise to three successive structures emerging rostrocaudally in the intermediate mesoderm. Nephrotomes first develop in the cervical part of the embryo; they consist in a ciliated funnel emerging in the coelomic cavity and in a nephritic tubule Int. J. Dev. Biol. 53: 411-424 (2009) doi: 10.1387/ijdb.082680jm connected to a common excretory duct (the Wolffian duct, WD). At this stage, they form a primitive kidney called pronephros which is not functional. This transitory organ can only be observed in vertebrate embryos and agnathe larvae (Saxen and Sariola 1987;Bouchard et al. 2002). Then, while the pronephros is regressing, the mesonephros develops posteriorly, allowing the WD to grow in the same direction. This intermediary kidney, comprising a Bowman ...

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“…Similar abnormalities have been described in discs, large homolog 1 (Dlgh1) null mice, who experience aplasia of the cervix and vagina from failed lateral fusion of the Müllerian ducts [23]. Transcriptional cofactors dachshund homolog 1 and 2 (Dach1 and Dach2) seem to fit within this developmental cascade as the double knock out mouse model shows complete failure to develop Müllerian duct derivatives [24]. Following Müllerian duct formation, differentiation occurs along an antero-posterior (A-P) and radial axis.…”

Section: Genes Responsible For Müllerian Duct Formation and Diferentimentioning

confidence: 60%

Genetic Syndromes and Genes Involved in the Development of the Female Reproductive Tract: A Possible Role for Gene Therapy

Owen¹,

JH²

2013

J Genet Syndr Gene Ther

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Müllerian and vaginal anomalies are congenital malformations of the female reproductive tract resulting from alterations in the normal developmental pathway of the uterus, cervix, fallopian tubes, and vagina. The most common of the Müllerian anomalies affect the uterus and may adversely impact reproductive outcomes highlighting the importance of gaining understanding of the genetic mechanisms that govern normal and abnormal development of the female reproductive tract. Modern molecular genetics with study of knock out animal models as well as several genetic syndromes featuring abnormalities of the female reproductive tract have identified candidate genes significant to this developmental pathway. Further emphasizing the importance of understanding female reproductive tract development, recent evidence has demonstrated expression of embryologically significant genes in the endometrium of adult mice and humans. This recent work suggests that these genes not only play a role in the proper structural development of the female reproductive tract but also may persist in adults to regulate proper function of the endometrium of the uterus. As endometrial function is critical for successful implantation and pregnancy maintenance, these recent data suggest a target for gene therapy. Future research will be needed to determine if gene therapy may improve reproductive outcomes for patients with demonstrated deficient endometrial expression related to abnormal gene expression.

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Mouse Dach1 and Dach2 are redundantly required for Müllerian duct development

Cited by 44 publications

References 45 publications

Molecular Genetics of Müllerian Duct Formation, Regression and Differentiation

Molecular Genetics of Müllerian Duct Formation, Regression and Differentiation

The developing female genital tract: from genetics to epigenetics

Genetic Syndromes and Genes Involved in the Development of the Female Reproductive Tract: A Possible Role for Gene Therapy

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