Differential expression patterns of Wnt genes in the murine female reproductive tract during development and the estrous cycle

Miller, Cary; Pavlova, Anna; Sassoon, David

doi:10.1016/s0925-4773(98)00112-9

Cited by 156 publications

(127 citation statements)

References 29 publications

Supporting

Mentioning

117

Contrasting

Unclassified

Order By: Relevance

“…Since SFRP-2 negatively regulates Wnt functions, it is envisioned that its down-regulation by estrogen allows Wnt-frizzled signaling to execute specific uterine functions. Wnt ligands participate in mesenchymal-epithelial interactions (66), and uterine expression of Wnt ligands (Wnt-4, Wnt-5a, and Wnt-7) is tightly regulated during the estrous cycle by estrogen and/or P 4 (67,68). Since Wnts regulate cellular proliferation, differentiation, and/or reorganization, we suggest that they act as estrogen-mediated transducers of these events in the uterus.…”

Section: Fig 8 Effects Of P 4 On Estrogen-induced Uterine Expressiomentioning

confidence: 87%

Estrogen Targets Genes Involved in Protein Processing, Calcium Homeostasis, and Wnt Signaling in the Mouse Uterus Independent of Estrogen Receptor-α and -β

Das¹,

Tan²,

Raja³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

Estrogen actions in target organs are normally mediated via activation of nuclear estrogen receptors (ERs). By using mRNA differential display technique, we show, herein, that estradiol-17␤ (E 2 ) and its catechol metabolite 4-hydroxy-E 2 (4OHE 2 ) can modulate uterine gene expression in ER␣(؊/؊) mice. Whereas administration of E 2 or 4OHE 2 rapidly up-regulated (4 -8-fold) the expression of immunoglobulin heavy chain binding protein (Bip), calpactin I (CalP), calmodulin (CalM), and Sik similar protein (Sik-SP) genes in ovariectomized wildtype or ER␣(؊/؊) mice, the expression of secreted frizzled related protein-2 (SFRP-2) gene was down-regulated (4-fold). Bip, CalP, and CalM are calcium-binding proteins and implicated in calcium homeostasis, whereas SFRP-2 is a negative regulator of Wnt signaling. Bip and Sik-SP also possess chaperone-like functions. Administration of ICI-182,780 or cycloheximide failed to influence these estrogenic responses, demonstrating that these effects occur independent of ER␣, ER␤, or protein synthesis. In situ hybridization showed differential cell-specific expression of these genes in wild-type and ER␣(؊/؊) uteri. Although progesterone can antagonize or synergize estrogen actions, it had minimal effects on these estrogenic responses. Collectively, the results demonstrate that estrogens have a unique ability to influence specific genes in the uterus not involving classical nuclear ERs.Estrogens regulate diverse physiological responses including normal functioning of the reproductive and cardiovascular systems and bone metabolism (1-3). The uterus is a primary target for various estrogenic responses during the cycle and pregnancy. In the mouse, estrogen induces uterine epithelial cell proliferation, and together with progesterone (P 4 ) 1 it directs stromal cell proliferation and epithelial cell differentiation. These coordinated estrogen and P 4 interactions prepare the uterus to the receptive state for implantation (reviewed in Ref. 4). The mechanism by which estrogen renders the P 4 -primed uterus receptive for implantation is not clearly understood.Estrogen actions are primarily executed by its binding to nuclear estrogen receptors, ER␣ and/or ER␤, which are ligandinducible transcription factors (5, 6). They modulate transcription of genes by virtue of their binding as hormone receptor complexes to specific DNA sequences (hormone response elements) in target promoters (5, 6). Despite the classical estrogenic actions, there is increasing evidence that gene transactivation or modulation of cell functions by estrogens is also mediated independent of nuclear ERs (7-10). In many cells, a myriad of estrogenic effects occurs rapidly within seconds or minutes. These responses do not require RNA or protein synthesis and are considered to be mediated by estrogen binding to the plasma membrane (10 -12). For example, increases in intracellular cAMP, calcium influx, inositol triphosphate, and release of prolactin are all attributed to membrane-mediated estrogen actions (10 -12). Although the pre...

show abstract

Section: Fig 8 Effects Of P 4 On Estrogen-induced Uterine Expressiomentioning

confidence: 87%

Estrogen Targets Genes Involved in Protein Processing, Calcium Homeostasis, and Wnt Signaling in the Mouse Uterus Independent of Estrogen Receptor-α and -β

Das¹,

Tan²,

Raja³

et al. 2000

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Noncanonical WNT signaling encompasses a variety of signaling pathways that involve different WNT receptors (i.e., ROR2 and RYK) and mediators (i.e., calcium, MAPK8/9/10, and CAMK2) that regulate cell migration and movement. A subset of Wnts (Wnt4, Wnt5a, and Wnt7a) is involved in müllerian duct patterning and differentiation during development of the female reproductive tract in the embryo [14,19,20]. Postnatal uterine morphogenesis also involves a number of different Wnts and their signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

Postnatal Deletion of Wnt7a Inhibits Uterine Gland Morphogenesis and Compromises Adult Fertility in Mice.

Dunlap¹,

Filant²,

Hayashi³

et al. 2011

Biology of Reproduction

View full text Add to dashboard Cite

The success of postnatal uterine morphogenesis dictates, in part, the embryotrophic potential and functional capacity of the adult uterus. The definitive role of Wnt7a in postnatal uterine development and adult function requires a conditional knockout, because global deletion disrupts mü llerian duct patterning, specification, and cell fate in the fetus. The Wnt7a-null uterus appears to be posteriorized because of developmental defects in the embryo, as evidenced by the stratified luminal epithelium that is normally found in the vagina and the presence of short and uncoiled oviducts. To understand the biological role of WNT7A after birth and allow tissue-selective deletion of Wnt7a, we generated loxP-flanked exon 2 mice and conditionally deleted Wnt7a after birth in the uterus by crossing them with Pgr Cre mice. Morphological examination revealed no obvious differences in the vagina, cervix, oviduct, or ovary. The uteri of Wnt7a mutant mice contained no endometrial glands, whereas all other uterine cell types appeared to be normal. Postnatal differentiation of endometrial glands was observed in control mice, but not in mutant mice, between Postnatal Days 3 and 12. Expression of morphoregulatory genes, particularly Foxa2, Hoxa10, Hoxa11, Msx1, and Wnt16, was disrupted in the Wnt7a mutant uteri. Conditional Wnt7a mutant mice were not fertile. Although embryos were present in uteri of mutant mice on Day 3.5 of pregnancy, blastocyst implantation was not observed on Day 5.5. Furthermore, expression of several genes (Foxa2, Lif, Msx1, and Wnt16) was reduced or absent in adult Wnt7a-deleted uteri on Day 3.5 postmating. These results indicate that WNT7A plays a critical role in postnatal uterine gland morphogenesis and function, which are important for blastocyst implantation and fertility in the adult uterus.developmental biology, female reproductive tract, pregnancy, transgenic/knockout model, uterus

show abstract

“…In the endometrium, Wnt7a functions in cell-cell communication and is responsive to changes in levels of sex steroid hormones [19]. Our lab has found that Wnt7a interacts with Fzd5 to activate β-catenin/canonical signaling and induce proliferation in endometrial cancer cells [Carmon and Loose, unpublished].…”

mentioning

confidence: 99%

Wnt7a interaction with Fzd5 and detection of signaling activation using a split eGFP

Carmon

Loose

2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

Wnts are secreted glycoproteins that regulate important cellular processes including proliferation, diiferentiation, and cell fate. In the β-catenin/canonical pathway, Wnt interacts with Fzd receptors to inhibit degradation of β-catenin and promote its translocation into the nucleus where it regulates transcription of a number of genes. Dysregulation of this pathway has been attributed to a host of diseases including cancer. As a result, components of the β-catenin/canonical pathway have been gaining recognition as promising targets for the discovery of novel therapeutic agents. Here we show, using an ELISA-based protein-protein binding assay that purified Wnt7a binds to the extracellular cysteine-rich domain of Fzd5 in the nanomolar range. We have developed a novel split eGFP complementation assay to visually detect Wnt7a-Fzd5 interactions and subsequent pathway activation in cells. These biological tools could help lead to a better understanding of Wnt-Fzd interactions and the identification of new modulators of Wnt signaling. KeywordsWnt signaling; Wnt7a; Fzd5; split eGFP; protein complementationThe β-catenin/canonical Wnt pathway defines a series of events that occur when Wnt proteins bind to cell-surface receptors of the Frizzled (Fzd) family. Currently, 19 Wnt proteins and 10 different Fzd members have been identified in the human genome[1;2]. The Wnt-Fzd interaction promotes complex formation with a membrane-associated Lrp 5/6 co-receptor and activates signaling through the direct recruitment of a Dishevelled (Dsh) protein to the intracellular portion of Fzd[3;4]. Dsh inhibits GSK-3 association with the Axin/APC complex of proteins that normally mark β-catenin for proteolytic degradation [5]. Intracellular pools of cytoplasmic β-catenin become stabilized, enter into the nucleus, and interact with the TCF/ LEF family of transcription factors to promote specific gene expression [6;7]. The Wnt-Fzd interaction has also been shown to activate two distinct non-canonical pathways; the planar cell polarity/JNK pathway and a Ca 2+ -mediated pathway[2;8;9].Wnt was initially discovered as a proto-oncogene in mammary tumors activated by integration of the mouse mammary tumor virus [10]. More recently, studies have linked the β-catenin/ canonical Wnt signaling pathway to disease onset and tumorogenesis [11][12][13]. The development of cancer has been attributed to mutations resulting in constitutive activation of *Corresponding Author: Phone: 713-500-7440, Fax: 713-500-7455, David.S.Loose@uth.tmc.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Me...

show abstract

Differential expression patterns of Wnt genes in the murine female reproductive tract during development and the estrous cycle

Cited by 156 publications

References 29 publications

Estrogen Targets Genes Involved in Protein Processing, Calcium Homeostasis, and Wnt Signaling in the Mouse Uterus Independent of Estrogen Receptor-α and -β

Estrogen Targets Genes Involved in Protein Processing, Calcium Homeostasis, and Wnt Signaling in the Mouse Uterus Independent of Estrogen Receptor-α and -β

Postnatal Deletion of Wnt7a Inhibits Uterine Gland Morphogenesis and Compromises Adult Fertility in Mice.

Wnt7a interaction with Fzd5 and detection of signaling activation using a split eGFP

Contact Info

Product

Resources

About