Journal
REPRODUCTIVE TOXICOLOGY
Volume 19, Issue 4, Pages 479-485Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2004.11.013
Keywords
cadmium; postaxial forelimb ectrodactyly; sonic hedgehog; polarizing activity; Gli/luciferase reporter; patched; Fgf8; Gli3
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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. (c) 2004 Elsevier Inc. All rights reserved.
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