Adherens junction breakdown in the periderm following cadmium administration in the chick embryo: distribution of cadherins and associated molecules.
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 4h 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 50microl of 50microM Cd solution at 60h 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 6microm sections treated according to standard protocols for immunohistochemical detection of L-CAM, pan-cadherin, beta-catenin, alpha-1 and alpha-2 catenin. To examine actin distribution, frozen sections were cut at 10-20microm, stained with oragon green phalloidin and nuclei counter-stained with propidium iodide.


RESULTS
The overall tissue distribution of L-CAM, pan-cadherin and the alpha-catenins did not appear to be altered following Cd. However, beta-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 4h.


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 beta-catenin to translocate to the nucleus in peri-ectodermal tissue, mimicking the canonical Wnt pathway.
Thompson
Jennifer
J
School of Medicine and Medical Science and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland. Jennifer.Thompson@ucd.ie
Wong
Laifen
L
Lau
Puong Sing
PS
Bannigan
John
J
D000199:Actins / Q000378:metabolism*; D021581:Active Transport, Cell Nucleus; D022005:Adherens Junctions / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002104:Cadmium / Q000633:toxicity*; D051177:Catenins / Q000378:metabolism*; D002642:Chick Embryo; D002645:Chickens; D005855:Germ Layers / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D013194:Staining and Labeling / Q000379:methods; D013997:Time Factors; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D051177:Catenins; D051178:alpha Catenin; D051176:beta Catenin; D002104:Cadmium