title: Disruption of noncanonical Wnt/CA2+ pathway in the cadmium-induced omphalocele in the chick model.
abstract: OBJECTIVE
  Cadmium (Cd) has been found to cause ventral body wall defects (VBWDs) in the chick embryo similar to human omphalocele. The earliest detectable histologic changes in Cd-induced VBWD chick model have been observed 4 hours posttreatment. The exact mechanism by which Cd acts in the early embryogenesis remains unclear. Wnt proteins play a key role during embryogenesis, and altered Wnt signaling has been linked to developmental defects. Noncanonical Wnt/Ca(2+) pathway has been implicated in regulating embryogenesis by controlling cell movement and adhesion. Wnt11 can activate protein kinase C (PKC) and calcium/calmodulin-dependent kinase II (CaMKII) in the Wnt/Ca(2+) pathway. We hypothesized that the Wnt11, PKCalpha, and CaMKII gene expression is downregulated in the Cd-induced VBWD during early embryogenesis.
  
  
  METHODS
  After 60 hours of incubation, chick embryos were harvested 1 hour (1H), 4H, and 8H after treatment of saline or cadmium and divided into 2 groups: control and Cd (n = 8 at each time-point, respectively). Real-time polymerase chain reaction was performed to evaluate the messenger RNA (mRNA) expression of Wnt11, PKCalpha, and CaMKII in the Cd-induced VBWD chick model.
  
  
  RESULTS
  The mRNA expression levels of Wnt11, PKCalpha, and CaMKII were significantly decreased at 1H in Cd group compared to controls (P < .05). However, there were no significant differences in the other time-points.
  
  
  CONCLUSIONS
  Downregulation of Wnt11, PKCalpha, and CaMKII gene expression during the narrow window of early embryogenesis may cause VBWD, interfering with cell movement and adhesion, disrupting Wnt/Ca(2+) pathway.
authors: The Children's Research Center, Our Lady's Children's Hospital, Dublin, Ireland.
authors: Takashi
authors: T
authors: Doi
authors: Prem
authors: P
authors: Puri
authors: John
authors: J
authors: Bannigan
authors: Jennifer
authors: J
authors: Thompson
mesh_terms: D034861:Abdominal Wall / Q000196:embryology*; D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002642:Chick Embryo; D004195:Disease Models, Animal; D015536:Down-Regulation; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006554:Hernia, Umbilical / Q000139:chemically induced / Q000196:embryology* / Q000503:physiopathology; D006801:Humans; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology
chemical_list: D051153:Wnt Proteins; C540523:Wnt11 protein, human; D002104:Cadmium; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium