Skn and ShhC25S mutants have defective long-range Hedgehog signaling in the limb. (A,A′,C,C′,E,E′,G,G′) Fore- and hindlimb skeletons of wild-type, Skn-/-, ShhC25S, and Shh-/- 18.5-dpc embryos stained with Alcian blue and Alizarin red. All views are dorsal. The axis for orientation of the specimens is posterior on the right, anterior on the left, proximal downward, and distal upward. (B,B′,D,D′,F,F′) Hematoxylin-and-eosin-stained sections through the distal ulnar and tibia of wild-type, Skn-/-, ShhC25S, and Shh-/- 18.5-dpc embryos. Arrows indicate immature chondrocytes. (H-U) Whole-mount in situ hybridization, using digoxigenin-labeled riboprobes on wild-type and Skn-/- limbs at 10.5 dpc. Bmp4 expression in Skn-/- limbs cannot be distinguished from that in wild-type limbs (Jones et al. 1991).