E-CADHERIN TRANSFORMS EMBRYONIC CORNEAL FIBROBLASTS TO STRATIFIED EPITHELIUM WITH DESMOSOMES

Important and precisely regulated transitions in tissue phenotype from epithelium to mesenchyme and from mesenchyme to epithelium occur in t he developing embryo. The gene for E-cadherin has been shown to cause fibroblastic cell lines to become epithelioid in culture. We asked whe ther or not the activities of the E-cadherin gene could cause a defini tive embryonic mesenchyme to transdifferentiate into an epithelial phe notype. Primary corneal fibroblasts from 6-to 7-day-old chick embryos were cotransfected by impact loading with plasmids containing E-cadher in and Neo' genes and selected in G418, The fibroblasts expressing E-c adherin aggregate, localize E-cadherin to lateral surfaces, and form s tratified epithelia that develop zonulae occludentes and adherentes, c onnexin 43, cytokeratin, desmoplakin, and desmosomes. Vimentin interme diate filaments persist and no basement membranes appear, even though the cells synthesize laminin and type IV collagen. Our study is the fi rst to demonstrate the ability of E-cadherin to induce fibroblasts to form desmosomes and stratified epithelia, The primary embryonic fibrob lasts apparently have more developmental potential to transdifferentia te into epithelia than do the fibroblastic cell lines previously studi ed. We conclude that E-cadherin is likely to play an important role in transformation of mesenchyme to epithelium in the embryo.