Cadmium-induced postaxial forelimb ectrodactyly: association with altered sonic hedgehog signaling

Administration of CdSO4 to C57BL/6 mice at day 9.5 of gestation induces a high incidence of postaxial forelimb ectrodactyly in the offspring. We propose that Cd2+ exposure impairs the process of anterior/posterior formation in the limb bud, a process that is directed by Sonic hedgehog (Shh) signaling. We show that exposure of the mouse embryo to Cd2+ disrupts Shh signaling as measured by polarizing activity of mouse limb bud ZPA grafted to a host chick wing, and activity of a Gli:luciferase reporter exposed to limb bud lysates. Yet the expression of Shh and its translation are not affected by Cd2+ exposure. We propose that teratogen exposure affects the processing of Shh in the cells in which it is made.