High impact information on Wnt11

• Treating the mouse embryonic carcinoma stem cell line P19 with murine Wnt-11 conditioned medium triggers cardiogenesis, which indicates that the function of Wnt-11 in heart development has been conserved in higher vertebrates [1].
• By contrast, when S-GAGs synthesis is not inhibited, BMP4 beads inhibit ureter branching and expression of Wnt 11, a target of glial cell-derived neurotrophic factor signaling [2].
• Studies of Wnt11 and Fras1/Grip1, all expressed in the ureteric bud, show a role for these genes in regulating events in the adjacent metanephric mesenchyme [3].
• The experimentally induced dysmorphology associated with deregulated expression of Wnt11, Gdnf and Fgf7 genes in the early stages of organogenesis indicated a crucial role for sprouty function in coordination of epithelial-mesenchymal and stromal signalling, the sites of expression of these genes [4].
• Wnt11 functions, in part, by maintaining normal expression levels of the gene encoding glial cell-derived neurotrophic factor (Gdnf) [5].

Biological context of Wnt11

• Mutation of the Wnt11 gene results in ureteric branching morphogenesis defects and consequent kidney hypoplasia in newborn mice [5].
• Wnt11, a member of the Wnt superfamily of secreted glycoproteins, which have important regulatory functions during vertebrate embryonic development, is specifically expressed in the tips of the branching ureteric epithelium [5].
• Upregulation of Wnt11 is temporally coordinated with the surge of maternal estradiol on Day 4 [6].
• Based on these results, we propose that Wnt11 plays an important role for cardiac development by embryoid bodies, and may be a key regulator of cardiac muscle cell proliferation and differentiation during heart development [7].
• A phylogenetic analysis of all known full-length Wnt11 sequences indicates that a gene duplication occurred at the base of the vertebrate Wnt11 clade [8].

Anatomical context of Wnt11

• Wnt11 repressed Wnt1-mediated activation of LEF-1 reporter activity in both cell lines [9].
• Wnt11 is expressed in the epithelium of esophagus and colon, but also in mesenchymal cells of the stomach [10].
• Wnt11 fails to be upregulated in blastocysts obtained from mice ovariectomized early on Day 4 or from mice treated with the estradiol antagonist, ICI 182,780 [6].
• Herein, we describe the role of Wnt11 during cardiac differentiation of embryonic stem cells [7].
• Proteoglycans are required for maintenance of Wnt-11 expression in the ureter tips [11].

Associations of Wnt11 with chemical compounds

• Moreover, in both cell types, elevation of intracellular Ca(2+) levels, which can result from Wnt11 treatment, led to the inhibition of canonical signaling [9].
• Administration of estradiol-17beta or its metabolite, 4-OH-estradiol, to ovariectomized mice restores Wnt11 expression [6].
• First, we examined the expression profile of Wnt11 during the course of differentiation in embryoid bodies, and then compared its expression in retinoic acid-treated embryoid bodies with that in untreated [7].
• Here we demonstrate that Wnt-4, a secreted glycoprotein which is required for tubule formation, is sufficient to trigger tubulogenesis in isolated metanephric mesenchyme, whereas Wnt-11 which is expressed in the tip of the growing ureter is not [12].
• The Wnt-11 gene encodes Cys-rich secretory protein distantly related to Wnt-1 through Wnt-8 from the mouse and Xenopus [13].

Other interactions of Wnt11

• Co-culture experiments with NIH3T3 cells showed that the co-expression of Wnt11 with Wnt1 was not an essential requirement for the inhibition, suggesting receptor competition as a possible mechanism [9].
• 5. Wnt11 is highly expressed at the gastro-esophageal junctions, while Wnt4 is found in the epithelium lining the pyloric region of the stomach but not in the epithelium of the prospective gland region [10].
• Wnt7a was mapped to mouse Chr 6, Wnt5a to the centromeric region of Chr 14, and Wnt11 to Chr7 [14].
• Other members expressed are Wnt2b, Wnt5b, and Wnt11 [15].
• However, Wnt11 was unable to inhibit canonical signaling activated by LRP5, Dvl1, or beta-catenin in NIH3T3 cells, although it could in P19 cells [9].

Analytical, diagnostic and therapeutic context of Wnt11

• Moreover, Wnt11 expression is not upregulated when blastocysts are trapped in the oviduct following ligation of the utero-tubal junction, nor when estradiol-17beta or 4-OH-estradiol are administered to blastocysts in vitro [6].
• We have isolated a new member of the Wnt gene family, Wnt-11, from chick embryo cDNA library and examined the expression pattern during embryogenesis by in situ hybridization [13].
• Northern blot analysis indicates the Wnt-4 expression at 1.5 kilobase and the Wnt-11 expression at 2.0 kilobase in the chick embryo [16].

References