Ureteric bud and distal ureter morphogenesis are severely disturbed in embryos with enhanced GDNF levels. Whole-mount calbindin staining of E10.5 (A) wild type (WT) and (B) Gdnf hyper/hyper urogenital blocks. Red lines show the width of the primary bud, yellow arrow points to normal (WT) and expanded (Gdnf hyper/hyper) end of nephric duct. Whole mount E-cadherin staining of E12.5 (C) WT and (D) Gdnf hyper/hyper urogenital blocks. Ureteric bud tips are depicted by yellow, dotted lines, arrowheads point to common nephric duct, which failed to start remodeling in Gdnf hyper/hyper urogenital system, white arrow shows the distinction of ureter from nephric duct in WT control (C’). Red arrow in C indicates the side where vertical displacement has completely occurred, yellow arrows show extra ureteric budding near to cloaca in the posterior nephric duct (D, D’). (E) E14.5 WT sample stained with E-cadherin (green) and cleaved-Caspase3 (red) shows normal ureteric buds (yellow, dotted lines) and ureters connecting to the lateral sides of upper bladder (white dotted line pointed by white arrow), while (F) in Gdnf hyper/hyper embryos ureters show large extension-like extra buds (yellow arrows) that connect to sex ducts (white arrow) and dilatated ureteric bud tips (yellow, dotted lines). Abbreviations: C; cloaca, g; gut, M; mesonephric duct, N; nephric duct, U; ureter. Scale bars: 200 µm.