Fig. 7. Ectopic BMP signaling induces ureter morphogenesis in zones of the UB normally fated to differentiate into collecting tubules. Whole-mount images of E12.5 (A-F) or 14.5 (G-J) metanephric explants cultured for 4 days in the absence (A,B,G,H) or presence (C-F,I,J) of recombinant BMP4. The UB network is labeled with antibodies directed against E-cadherin (red, A-F; blue, G-J), differentiated ureter epithelia identified by uroplakin expression (A,C,E, green; G-J, red) and the ureteral smooth muscle coat visualized by SMA expression (B,D,F,H, green). (J) Enlargement of framed area in I. In control cultures (A,B,G,H), ureter differentiation occurs only in the distal-most domain of the UB (arrowheads) as determined by upregulated uroplakin expression (A,G) and formation of a well-organized SMA-positive (B,G) coat. SMA-positive cells can also be detected between medullary collecting tubules (ml), but are not organized into a dense connective investment around the tubules in this location. Both uroplakin-positive cells (B,E,I,J) and an SMA-positive connective tissue investment can be detected in more proximal zones of the UB (pUB) network (^* referring to proximal domains of UB network) when cultures are maintained with 25 ng/ml (C,D) or 100 ng/ml BMP4 (E,F,I,J).