BMPR1A-mediated BMP1 signalling is disrupted in the cadmium-induced omphalocele in the chick model.
OBJECTIVE
In the chick embryo, administration of cadmium (Cd) induces omphalocele phenotype. The earliest histological changes in this model are observed commencing at 4-h post treatment (4H). The molecular mechanisms by which Cd acts during the critical period of embryogenesis remain unclear. Bone morphogenetic proteins (BMPs) and their receptors (BMPRs) regulate many fundamental biological processes and are involved in various embryonic morphogenesis, including ventral body wall (VBW) formation. Homozygous BMP1 mutant mice cause VBW defects. It has been reported that BMPR1A conditional knockouts also exhibit omphalocele phenotype. We designed this study to test the hypothesis that gene expression levels of BMP1 and BMPR1A are downregulated during the critical period of embryogenesis in the Cd chick model.


METHODS
After 60-h incubation, chick embryos were exposed to either Cd or saline and then harvested 1H, 4H and 8H. Chicks were divided into control (n = 24) and Cd (n = 24). RT-PCR was performed and differences between the two groups were tested statistically (significance was accepted at p < 0.05). Immunohistochemical study was also performed to evaluate those proteins expression/distribution.


RESULTS
The gene expression levels of BMP1 and BMPR1A at 4H were significantly downregulated in Cd group compared to controls. Immunoreactivity of BMP1 and BMPR1A was also markedly decreased in Cd-treated embryos compared to controls.


CONCLUSIONS
Disruption of BMPR1A-mediated BMP1 signalling during the narrow window of early embryogenesis may interfere with normal VBW formation, causing omphalocele phenotype in the Cd chick model.
National Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Ireland.
Takashi
T
Doi
Prem
P
Puri
John
J
Bannigan
Jennifer
J
Thompson
D000818:Animals; D055395:Bone Morphogenetic Protein 1 / Q000235:genetics* / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D002104:Cadmium / Q000633:toxicity; D002642:Chick Embryo; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006554:Hernia, Umbilical / Q000196:embryology / Q000201:enzymology / Q000235:genetics*; D007150:Immunohistochemistry; D010641:Phenotype; D012313:RNA / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
D002104:Cadmium; D012313:RNA; D052005:Bone Morphogenetic Protein Receptors, Type I; D055395:Bone Morphogenetic Protein 1
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