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Fig. 6. Wnt5a is required for the uterotrophic response and for DES-mediated repression of Wnt7a. Neonate (P0) uterine horns from control and Wnt5a-/- individuals were separated into two pools of grafts that were grown in two ovariectomized hosts for 3 weeks. Each host received control (two left-hand columns) and mutant (two right-hand columns) grafts. For each experiment, one host was injected intraperitoneally daily from day 18 to day 20 with DES resuspended in saline and one host was injected with saline alone, as indicated. Hosts were sacrificed on day 21 and the grafts harvested for analyses. Results are shown for a Wnt5a+/– individual and a Wnt5a-/- individual. (A-H) Haematoxylin-Eosin staining at low magnification (A-D; scale bar: 250 µm) and high magnification (E-H; scale bar: 20 µm). Note the aberrant uterotrophic response in the Wnt5a-/- graft (D) showing enlarged lumen and thin uterine walls when compared with the Wnt5a+/– graft (B). The Wnt5a-/- epithelium does show an increase in height and thickness in response to DES (H). (I-T) In situ hybridization for Wnt7a (I-L), Hoxa10 (M-P) and Hoxa11 (Q-T). Wnt7a is repressed by DES in the Wnt5a+/– control graft (J) but not in the mutant (L). Hoxa10 and Hoxa11 are strongly repressed by DES in the subepithelial stroma of the Wnt5a+/– control graft (N,R) but not in the Wnt5a-/- graft (P,T). Lines delineate the limits between the luminal epithelium, the stroma and the myometrium.





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