Disruption of calreticulin-mediated cellular adhesion signaling in the cadmium-induced omphalocele in the chick model.
OBJECTIVE
Administration of cadmium (Cd) causes omphalocele in the chick embryo. The earliest histological changes in the chick Cd model are the breakdown of adherens junctions (AJs). Calreticulin (CRT) plays a key role in Ca(2+) signaling and cell adhesion. Ca(2+) signaling in the Cd chick model is known to be altered. The calcium-dependent adhesion molecule, E-cadherin, and its associate, beta-catenin, are key components of AJs regulated by CRT. CRT knockouts display omphalocele. We hypothesized that CRT, E-cadherin and beta-catenin are downregulated during early embryogenesis in the Cd chick model.


METHODS
After 60 h (H) incubation, chicks were harvested 1H, 4H, and 8H post treatment with saline or Cd and divided into controls and Cd. RT-PCR was performed to evaluate mRNA levels of CRT, E-cadherin and beta-catenin in the Cd chick model.


RESULTS
The mRNA levels of CRT were significantly decreased in the Cd group at 1H compared to controls (p < 0.05). The mRNA levels of E-cadherin and beta-catenin were significantly decreased at 4H in the Cd group compared to controls (p < 0.05). There were no significant differences at 8H.


CONCLUSIONS
Downregulation of CRT, E-cadherin and beta-catenin genes may cause omphalocele in the Cd chick model by disrupting CRT-mediated Ca(2+) signaling and AJs.
The 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; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002104:Cadmium / Q000633:toxicity; D064032:Calbindin 2; D002448:Cell Adhesion / Q000502:physiology*; D002642:Chick Embryo; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006554:Hernia, Umbilical / Q000139:chemically induced / Q000196:embryology / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D064030:S100 Calcium Binding Protein G / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000096:biosynthesis / Q000235:genetics
D015820:Cadherins; D064032:Calbindin 2; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; D051176:beta Catenin; D002104:Cadmium