Adherens junction breakdown in the periderm following cadmium administration in the chick embryo: distribution of cadherins and associated molecules

Abstract

Background The teratogenic metal cadmium (Cd) has been found to cause ventral body wall defects similar to human omphalocele when administered to post-gastrulation chick embryos prior to body wall folding. From 4 h after Cd, affected embryos demonstrate varying degrees of cell junction breakdown and desquamation in the periderm. We examined the effect of Cd on tissue and cell distribution of cadherins and their intracellular associates. Methods Chicks were explanted and given 50 μl of 50 μM Cd solution at 60 h incubation (Hamburger-Hamilton stage 16–17). To examine peridermal junctions, embryos were processed into resin and ultra-thin sections examined by transmission electron microscopy (TEM). Tissue was processed into paraffin and 6 μm sections treated according to standard protocols for immunohistochemical detection of L-CAM, pan-cadherin, β-catenin, α-1 and α-2 catenin. To examine actin distribution, frozen sections were cut at 10–20 μm, stained with oragon green phalloidin and nuclei counter-stained with propidium iodide. Results The overall tissue distribution of L-CAM, pan-cadherin and the α-catenins did not appear to be altered following Cd. However, β-catenin changed from its normal sub-membranous location to a more general cytoplasmic distribution, with translocation to the nucleus in both peridermal and ectodermal cells. Similarly, actin distribution in the periderm in embryos demonstrating cell junction breakdown was markedly altered, with clumping and disorganization after 4 h. Conclusions Although L-CAM is distributed normally after Cd, post-translational modification may occur causing breakdown of its normal association with the catenins and actin, and allowing β-catenin to translocate to the nucleus in peri-ectodermal tissue, mimicking the canonical Wnt pathway.