Microarray analysis of murine limb bud ectoderm and mesoderm after exposure to cadmium or acetazolamide.
BACKGROUND
A variety of drugs, environmental chemicals, and physical agents induce a common limb malformation in the offspring of pregnant mice exposed on day 9 of gestation. This malformation, postaxial, right-sided forelimb ectrodactyly, is thought to arise via an alteration of hedgehog signaling.


METHODS
We have studied two of these teratogens, acetazolamide and cadmium, using the technique of microarray analysis of limb bud ectoderm and mesoderm to search for changes in gene expression that could indicate a common pathway to postaxial limb reduction.


RESULTS
Results indicated a generalized up-regulation of gene expression after exposure to acetazolamide but a generalized down-regulation due to cadmium exposure. An intriguing observation was a cadmium-induced reduction of Mt1 and Mt2 expression in the limb bud mesoderm indicating a lowering of embryonic zinc.


CONCLUSIONS
We propose that these two teratogens and others (valproic acid and ethanol) lower sonic hedgehog signaling by perturbation of zinc function in the sonic hedgehog protein.
Schreiner
Claire M
CM
Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, and Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio 45229, USA.
Bell
Sheila M
SM
Scott
William J
WJ
D000086:Acetazolamide / Q000633:toxicity*; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D004475:Ectoderm / Q000002:abnormalities / Q000187:drug effects*; D005260:Female; D005552:Forelimb / Q000002:abnormalities / Q000187:drug effects / Q000196:embryology; D053823:Hedgehog Proteins / Q000378:metabolism; D018878:Limb Buds / Q000002:abnormalities / Q000187:drug effects* / Q000196:embryology; D008648:Mesoderm / Q000002:abnormalities / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D013723:Teratogens / Q000633:toxicity*
D053823:Hedgehog Proteins; D013723:Teratogens; D002104:Cadmium; D000086:Acetazolamide