Figure 6. Ectopic ureter budding in Gata3^{ND−/ −} embryos depends on GDNF/Ret and Fgf signaling.

(A, B) E10.5 UGS organ cultures recapitulate the phenotype of both control and Gata3^{ND−/ −} embryos observed in vivo. (C, D) Treatment of cultures with the Ret kinase inhibitor SU5416 efficiently inhibits both primary (*) and ectopic budding in control and Gata3^{ND−/ −} UGSs. (E, F) Supplementing the organ cultures with recombinant GDNF induces ectopic ureteric budding in control UGS cultures (arrows in E) and enhances ectopic bud growth in Gata3^{ND−/ −} UGS cultures (arrows in F). (G, H) Organ culture of control or Gata3-deficient UGSs treated with a GDNF blocking antibody suppresses primary and ectopic bud formation, respectively. (I, J) Soluble FgfR2-Fc fusion protein has no major effect on primary budding in control UGSs, but successfully inhibits ectopic budding in Gata3^{ND−/ −} UGSs. ub, ureteric bud; *, primary bud agenesis.