title: Alteration of gene expression of IQGAP1 and Rho-family GTPases in the cadmium-induced ventral body wall defects in the chick model.
abstract: Cadmium (Cd) induces ventral body wall defects (VBWD) in the chick embryo, with adherens junctions (AJs) breakdown at 4h post treatment (4H). Signalling by which Cd disrupts AJs in this model remains unclear. IQGAP1 regulates AJs via binding to Cdc42 and Rac1, Rho-family GTPases. Activation of IQGAP1-Cdc42 interaction regulates AJs positively, whereas Rac1 activation inhibits AJs. We hypothesised that IQGAP1 and Cdc42 are downregulated and Rac1 is upregulated during embryogenesis in the Cd chick model. Chick embryos were explanted and treated with saline or Cd after 60 h incubation. Chicks were harvested at 1H, 4H and 8H post treatment and RT-PCR and immunohistochemistry were performed. Gene expression levels of IQGAP1 and Cdc42 were significantly downregulated and Rac1 was upregulated in Cd group compared to controls only at 4H. Immunoreactivity of IQGAP1 and Cdc42 was also markedly decreased, whereas Rac1 was increased in Cd group compared to controls at 4H. Alteration of IQGAP and Rho-family GTPases may cause VBWD in Cd chick model by inducing the dissociation of cadherin-mediated AJs.
authors.affiliation: National Children's Research Centre, Our Lady's Children's Hospital, Dublin 12, Ireland.
authors.forename: Takashi
authors.initials: T
authors.lastname: Doi
authors.forename: Prem
authors.initials: P
authors.lastname: Puri
authors.forename: John
authors.initials: J
authors.lastname: Bannigan
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thompson
mesh_terms: D000818:Animals; D019256:Cadmium Chloride / Q000633:toxicity*; D002642:Chick Embryo; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006554:Hernia, Umbilical / Q000139:chemically induced* / Q000196:embryology / Q000235:genetics; D013723:Teratogens / Q000633:toxicity*; D020830:rac1 GTP-Binding Protein / Q000235:genetics* / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D013723:Teratogens; D020703:ras GTPase-Activating Proteins; D020830:rac1 GTP-Binding Protein; D019256:Cadmium Chloride