Cadmium-induced postaxial forelimb ectrodactyly: association with altered sonic hedgehog signaling.
Administration of CdSO(4) to C57BL/6 mice at day 9.5 of gestation induces a high incidence of postaxial forelimb ectrodactyly in the offspring. We propose that Cd(2+) 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 Cd(2+) 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 Cd(2+) exposure. We propose that teratogen exposure affects the processing of Shh in the cells in which it is made.
Scott
William J
WJ
Division of Developmental Biology and the Department of Pediatrics, Children's Hospital Medical Center and the University of Cincinnati, Cincinnati, OH 45229-3039, USA. william.scott@cchmc.org
Schreiner
Claire M
CM
Goetz
John A
JA
Robbins
David
D
Bell
Sheila M
SM
D000818:Animals; D015153:Blotting, Western; D019521:Body Patterning; D019187:Cadmium Compounds / Q000633:toxicity*; D002642:Chick Embryo; D004475:Ectoderm / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D005260:Female; D005552:Forelimb / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism; D005865:Gestational Age; D053823:Hedgehog Proteins; D020287:In Situ Nick-End Labeling; D018878:Limb Buds; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013431:Sulfates / Q000633:toxicity*; D015534:Trans-Activators / Q000096:biosynthesis*; D038062:Upper Extremity Deformities, Congenital / Q000139:chemically induced / Q000196:embryology / Q000378:metabolism*; D014921:Wings, Animal / Q000196:embryology
D019187:Cadmium Compounds; D053823:Hedgehog Proteins; C465570:Shh protein, mouse; D013431:Sulfates; D015534:Trans-Activators; C037123:cadmium sulfate