Msx1 and Msx2 gene expression is downregulated in the cadmium-induced omphalocele in the chick model.
OBJECTIVE
The administration of cadmium (Cd) induces an omphalocele phenotype in the chick embryo. The molecular mechanism by which Cd acts still remains unclear. Msx1 and Msx2 are expressed in the developing body wall and regulate cellular proliferation and differentiation. It has been reported that Msx1/Msx2 double-mutant mice display an omphalocele phenotype. We hypothesized that gene expression levels of Msx1 and Msx2 are downregulated in the Cd chick model during the critical period of embryogenesis.


METHODS
After 60 hours of incubation, chick embryos were exposed to either Cd or saline and harvested at 1 hour (1H), 4H, and 8H after treatment. Chicks were divided into 2 groups: control and Cd (n = 8 for each group at each time-point). Real-time polymerase chain reaction was performed to evaluate the messenger RNA levels of Msx1 and Msx2 in the Cd-induced omphalocele chick model and analyzed statistically. Immunohistochemistry was also performed to examine protein expression of Msx1 and Msx2 at each time-point.


RESULTS
Messenger RNA expression levels of Msx1 and Msx2 at 1H were significantly decreased in the Cd group compared with controls (P < .01), whereas there were no significant differences at the other time-points. Immunoreactivity of Msx1 and Msx2 at 1H was remarkably decreased in Cd group compared with controls.


CONCLUSIONS
Downregulation of Msx1 and Msx2 gene expression during the narrow window of early embryogenesis may cause an omphalocele by disrupting cellular proliferation and differentiation in the developing body wall.
Doi
Takashi
T
The Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Ireland.
Puri
Prem
P
Bannigan
John
J
Thompson
Jennifer
J
D000818:Animals; D002104:Cadmium / Q000633:toxicity; D002642:Chick Embryo; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental; D006554:Hernia, Umbilical / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D007150:Immunohistochemistry; D051957:MSX1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C084119:MSX2 protein; D012333:RNA, Messenger; D002104:Cadmium