The Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein (Klingensmith et al., 1994)
that regulates cell proliferation, acting as a transducer molecule for developmental processes, including segmentation and neuroblast specification. Pizzuti et al. (1996) noted that dsh is required for the function of the wingless gene product wg, a segment polarity gene homologous to the mammalian protooncogene WNT1. Pizzuti et al. (1996) reported the isolation and chromosomal mapping of 2 human dsh homologs, designated DVL1 and DVL3. Utilizing RT-PCR with degenerate primers, Tsang et al. (1996) isolated a member of the mouse Dishevelled (Dvl) gene family, Dvl3. The Dvl3 gene maps to mouse chromosome 16. The predicted amino acid sequence shares 64 and 62% identity to Dvl1 and Dvl2, respectively. The region of highest conservation between all three Dvl coding regions, at 97% identity, is noted at the PDZ domain (also termed the DHR domain or GLGF motif), a motif of 60 amino acids present in all
dishevelled encoded proteins and first described in the Drosophila discs large (dlg) tumor suppressor gene.
NCBI Summary:
DVL3 is a member of multigene family that also contains DVL1 and DVL2. The vertebrate dishevelled proteins have approximately 40% amino acid sequence similarity with Drosophila dsh. DVL3 encodes a predicted 716-amino acid polypeptide that shows 74% nucleotide similarity with human DVL1. Similarity is particularly high in the N-terminal region and there is more divergence in the C-terminal regions. Charcot-Marie-Tooth type 2B maps to chromosome 3q. The mechanisms of dishevelled function in Wnt signaling are likely to be conserved among metazoans.
General function
Intracellular signaling cascade
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Cellular localization
Cytoplasmic
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Ovarian function
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Expression regulated by
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Ovarian localization
Oocyte, Cumulus
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Tsang et al. (1996) reported that in adult mice, Dvl3 expression is widespread with highest levels exhibited in brain, ovary, and heart. In embryos, Dvl3 is expressed in every tissue between 7.5 and 9.5 days postcoitum, and by 10.5 days postcoitum highest expression was seen in the dorsal root ganglia, somites, limb buds, branchial arches, heart, gut and throughout the developing central nervous system.Dishevelled proteins regulate cell adhesion in mouse blastocyst and serve to monitor changes in Wnt signaling. Na J et al. Wnt signaling is essential for the regulation of cell polarity and cell fate in the early embryogenesis of many animal species. Multiple Wnt genes and its pathway members are expressed in the mouse early embryo, raising the question whether they play any roles in preimplantation development. Dishevelled is an important transducer of divergent Wnt pathways. Here we show that three of the mouse Dishevelled proteins are not only expressed in oocytes and during preimplantation development, but also display distinct spatio-temporal localization. Interestingly, as embryos reach blastocyst stage, Dishevelled 2 becomes increasingly associated with cell membrane in trophectoderm cells, while at E4.5, Dishevelled 3 is highly enriched in the cytoplasm of ICM cells. These changes are coincident with an increase in the active form of beta-catenin, p120catenin transcription and decrease of Kaiso expression, indicating an upregulation of Wnt signaling activity before implantation. When Dishevelled-GFP fusion proteins are overexpressed in single blastomeres of the 4-cell stage embryo, the progeny of this cell show reduction in cell adhesiveness and a rounded shape at the blastocyst stage. This suggests that perturbing Dvl function interferes with cell-cell adhesion through the non-canonical Wnt pathway in blastocysts.
Follicle stages
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Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis. van Montfoort AP et al. Besides the established selection criteria based on embryo morphology and blastomere number, new parameters for embryo viability are needed to improve the clinical outcome of IVF and more particular of elective single embryo transfer (eSET). Genome-wide gene expression in cumulus cells was studied, since these cells surround the oocyte inside the follicle and therefore possibly reflect oocyte developmental potential. Early cleavage (EC) was chosen as a parameter for embryo viability. Gene expression in cumulus cells from eight oocytes resulting in an EC embryo (EC-CC; n=8) and from eight oocytes resulting in a non-EC (NEC) embryo (NEC-CC; n=8) was analysed using microarrays (n=16). A total of 611 genes were differentially expressed (P < 0.01), mainly involved in cell cycle, angiogenesis, apoptosis, epidermal growth factor, fibroblast growth factor and platelet-derived growth factor signalling, general vesicle transport and chemokine and cytokine signalling. Of the 25 selected differentially expressed genes analysed by quantitative real-time PCR (qRT-PCR) 15 (60%) genes could be validated in the original samples. Of these 8 (53%) could also be validated in 24 (12-EC-CC and 12 NEC-CC) extra independent samples. The most differentially expressed genes among these were CCND2, CXCR4 , GPX3 , CTNND1 DHCR7 , DVL3 , HSPB1 and TRIM28 , which probably point to hypoxic conditions or a delayed oocyte maturation in NEC-CC samples. This opens up perspectives for new molecular embryo or oocyte selection parameters which might also be useful in countries where the selection has to be made at the oocyte stage before fertilization instead of at the embryonic stage.