Disease relevance of Wnt10b

• In fresh tissues, all Wnt genes apart from Wnt10b were expressed in normal endometrium and endometrial carcinoma [1].
• Transgenic mice with expression of Wnt10b from the FABP4 promoter (FABP4-Wnt10b) have less adipose tissue when maintained on a normal chow diet and are resistant to diet-induced obesity [2].
• The gene is the human homologue of mouse Wnt10b, recently shown to be one of the oncogenes cooperating with FGF3 in the development of mouse mammary tumour virus (MMTV) induced mouse mammary carcinomas [3].
• Transgenic expression of Wnt1 or Wnt10b in the mouse mammary gland leads to lobuloalveolar hyperplasia with a major risk of progression to carcinoma [4].

High impact information on Wnt10b

• Here we show that Wnt signaling, likely mediated by Wnt-10b, is a molecular switch that governs adipogenesis [5].
• Activation of Wnt signaling by Wnt10b inhibits differentiation of preadipocytes and blocks adipose tissue development; however, the effect of Wnt10b on other mesenchymal lineages has not been defined [6].
• To explore the physiological role of Wnt signaling in bone development, we analyzed FABP4-Wnt10b mice, which express the Wnt10b transgene in marrow [6].
• Finally, Wnt10b-/- mice have decreased trabecular bone and serum osteocalcin, confirming that Wnt10b is an endogenous regulator of bone formation [6].
• In addition, FABP4-Wnt10b mice are protected from the bone loss characteristic of estrogen deficiency [6].

Biological context of Wnt10b

• In the zebrafish, Wnt1 and Wnt10b functionally overlap in their control of gene expression in the ventral midbrain-hindbrain boundary (MHB), but they are not required for the formation of the MHB constriction [7].
• Here, we identified and characterized rat Wnt1 and Wnt10b genes by using bioinformatics [8].
• Wnt1 and Wnt10b genes at rat chromosome 7q36 were clustered in head-to-head manner with an interval of about 10 kb within AC096835.4 or AC118760.4 genome sequences [8].
• GC content of rat Wnt1-Wnt10b IGCR (nucleotide position 14962-15875 of AC096835.4 genome sequence) was 59.4% [8].
• Rat Wnt10b gene, consisting of five exons, encoded a 389-aa protein with signal peptide, 24 conserved Cys residues and two Asn-linked glycosylation sites [8].

Anatomical context of Wnt10b

• Wnt10b was localised specifically to the presumptive dental epithelium [9].
• Reciprocal expression of Wnt10b with UCP1 and PGC-1alpha in interscapular tissue from cold-challenged or genetically obese mice provides further evidence for regulation of brown adipocyte metabolism by Wnt signaling [10].
• These expression patterns suggest that Wnt10a and Wnt10b may function in various tissues of the adult and embryo with notable expression in tissues responsible for the formation and maturation of blood cells, in the pituitary gland (Wnt10a), and in the face, limbs and skin of developing embryos [11].
• Wnt10a RNA was most abundant in adult brain with a high concentration in the pituitary gland, and expression of Wnt10b was highest in adult lung and uterus [11].
• To date, the formation of the mammary line expressing Wnt10b is the earliest discernible ectodermal event in murine embryonic mammary gland development [12].

Associations of Wnt10b with chemical compounds

• Embryos cultured in medium containing WNT3A or the WNT pathway activator lithium chloride (LiCl) display accelerated formation of expanded placodes, and LiCl induces the formation of ectopic placode-like structures that show elevated expression of the placode marker Wnt10b [13].
• Of the agents used to induce differentiation, exposure of 3T3-L1 cells to methyl-isobutylxanthine or cAMP is sufficient to suppress expression of Wnt10b mRNA [14].

Regulatory relationships of Wnt10b

• Wnt10b blocks brown adipose tissue development and expression of UCP1 when expressed from the fatty acid binding protein 4 promoter, even when mice are administered a beta3-agonist [10].
• Mimicking Wnt signaling in aged myoblasts through inhibition of glycogen synthase kinase or through overexpression of Wnt10b resulted in inhibition of adipogenic gene expression and sustained or enhanced myogenic differentiation [15].
• Wnt-5a and Wnt-10b were expressed in day-11 murine yolk sac, day-14 fetal liver, and fetal liver AA4+ cells [16].

Other interactions of Wnt10b

• Using reverse-transcriptase polymerase chain reaction analysis we identified several candidate Wnt genes whose expression pattern was consistent with a role in generation, maintenance and/or differentiation of early haematopoietic progenitor cells including three genes previously shown to have a role in haematopoiesis (Wnt5a, Wnt2b and Wnt10b) [17].
• Wnt10a and full length Wnt10b encode relatively closely related (62% identity) Wnt proteins containing the 24 cysteines characteristic of most Wnt proteins [11].
• We show here that a mammary line exists in the mouse embryo at embryonic day (E) 11.25 as a concise line of Wnt10b expression and a broader band of Wnt6 expression in the surface ectoderm, between the subaxillary and suprainguinal region of each flank [12].
• Consistent with these in vitro observations, UCP1-Wnt10b transgenic mice, which express Wnt10b in interscapular tissue, lack functional brown adipose tissue [10].
• Using a PCR-based approach, we have isolated two novel members of the murine Wnt gene family, Wnt11 and Wnt12 [18].

Analytical, diagnostic and therapeutic context of Wnt10b

• Wnt10a and Wnt10b expression broadly peaked at approximately 13.5 and 15.5 days of gestation, respectively, and Northern blot analyses of RNAs from dissected embryos revealed that expression of both genes was strongest in the face, limbs and skin and that Wnt10a was also expressed in the liver, the major site of hematopoiesis in the embryo [11].

References