Disease relevance of Wnt7b

• The level of expression of Wnt2 and Wnt4 was 10- to 20-fold higher in fibroadenomas than it was in normal or malignant breast tissue, and in 10% of tumors Wnt7b expression was 30-fold higher than in normal or benign breast tissues [1].
• Mice lacking Wnt7b gene die soon after birth because of respiratory failure and display severe lung hypoplasia [2].
• By using a murine retrovirus to ectopically express Wnt-7b in presumptive dental ectoderm in mandibular arch explants, we show that Shh expression in the ectoderm and Ptc expression in the underlying ectomesenchyme are down-regulated, and tooth development is subsequently arrested [3].

High impact information on Wnt7b

• Although exogenous overexpression of Dkk before the expression of endogenous canonical Wnt (Wnt7b) suppressed osteogenesis in cultures, its expression after peak Wnt7b expression induced a phenotype resembling terminal osteoblast differentiation leading to mineralization [4].
• In contrast, Wnt7b and Dvl activate Rac and JNK in hippocampal neurons [5].
• Here we show that Wnt7b, which is expressed in the mouse hippocampus, increases dendritic branching in cultured hippocampal neurons [5].
• We describe a reciprocal relationship between the expression of Wnt-7b in presumptive oral ectoderm and Shh in presumptive dental ectoderm in mouse embryos that mark boundaries between these cells with different developmental fates [3].
• Biochemical analysis demonstrates that Wnt7b can bind to Fzd1 and -10 on the cell surface and cooperatively activate canonical Wnt signaling with these receptors in the presence of LRP5 [6].

Biological context of Wnt7b

• Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis [7].
• Wnt7b is a Wnt ligand that has been demonstrated to play critical roles in several developmental processes, including lung airway and vascular development and chorion-allantois fusion during placental development [6].
• Cell transfection studies demonstrate that Wnt7b can activate the canonical Wnt pathway but not the noncanonical Wnt pathway in a cell-specific manner [6].
• At this stage, cortical progenitor cells start to loose their apical/basal cell polarity correlating with an ectopic expression of Wnt7b in the ventricular zone [8].
• Engrailed-2 also affects the transient mediolateral (M/L) pattern of En-1 and Wnt-7b expression seen in late embryogenesis [9].

Anatomical context of Wnt7b

• Wnt7a and Wnt7b mRNAs were expressed in three out of four cell lines (RL95-2, HEC-1-A and Ishikawa) [10].
• At least three genes (Wnt-3, Wnt-3a, and Wnt-7b) exhibit sharp boundaries of expression in the forebrain that may predict subdivisions of the region later in development [11].
• Wnt7b is expressed in the airway epithelium, suggesting a possible role for Wnt-mediated signaling in the regulation of lung development [12].
• In situ hybridizations with Wnt7b, a marker of the metanephric kidney, show that the branching defect was not simply the result of homeotic transformation of metanephros to mesonephros [13].
• Wnt7b expression in the chorion is required for fusion of the chorion and allantois during placental development [14].

Associations of Wnt7b with chemical compounds

• Whereas addition of suramin to COS cell cultures significantly increases the levels of all six Wnts in the medium, the addition of heparin only influences the levels of Wnt-1, Wnt-6, and Wnt-7b [15].

Other interactions of Wnt7b

• Mapping of closely linked genes in an interspecific backcross panel allowed us to exclude two previous candidate genes, Ly6 and Wnt7b [16].
• In 0.5% serum, growth of the Wnt-1, Wnt-6 and Wnt-7b containing cells appeared to be inhibited [17].
• Our results are also the first report of biological effects of Wnt-6 and Wnt-7b [17].
• Whereas Wnt10b deficiency contributed to increased adipogenic potential in myoblasts, the augmented myogenic differentiation potential observed is likely the result of a compensatory increase in Wnt7b during differentiation of Wnt10b-/- myoblasts [18].
• Furthermore, we found that expression of Wnt-7b, which overlapped with Pax-6 in the ventrolateral domain of the neural tube, was also specifically missing in the mutant hindbrain, while it remained intact in the dorsal non-overlapping domain [19].

Analytical, diagnostic and therapeutic context of Wnt7b

• Wnt-7b did not alter normal mammary gland development despite having similar effects to Wnt-1 in cell culture [20].

References