MEK inhibition rescues ureteric bud morphology in Gdnf hyper/hyper kidneys. (A) Wild type (WT) kidney cultured in mock medium for 48 h shows normal morphology of ureteric bud tips (arrows). (B) Similarly to published results39,41, inactivation of MAPK pathway by MEK inhibitor UO126 results in failure to expand ureteric bud tips (arrow) in WT kidneys. (C) Gdnf hyper/hyper kidney cultured in mock medium shows expanded ureteric bud tips and very short trunks. (D) MAPK pathway inhibition significantly improves both ureteric bud tip morphology and trunk length in Gdnf hyper/hyper kidneys. (E) Statistical analysis of UO126 treatment effects on trunk lengths in WT and Gdnf hyper/hyper kidneys shows that MEK inhibition significantly promotes trunk length in Gdnf hyper/hyper kidneys (411.69 ± 50.93 µm in Gdnf hyper/hyper kidneys cultured with UO126, 263.59 ± 29.55 µm in Gdnf hyper/hyper kidney cultured with DMSO, p = 0.047, n = 9, paired sample t-test; 448.01 ± 44.49 µm in WT kidney cultured with UO126, 484.03 ± 33.16 µm in WT kidney cultured with DMSO, p = 0.146, n = 3, paired sample t-test). Data presented as average trunk length ± the standard error of mean (SEM), *denotes P < 0.05 in paired sample t-test. Abbreviations: CND; common nephric duct, G; gut, ND; nephric duct. Scale bar: 200 µm.