Disruption of keratin filaments in embryonic epithelial cell types

Abstract

The murine keratins Endo B and Endo A, which are homologs of the human keratins K18 and K8, constitute the intermediate filaments (IFs) that are found in all simple epithelia of the adult and in the first epithelial derivatives of the early embryo. The cellular role of simple epithelial keratins in development and differentiation was investigated by inducing filament collapse in HR9 endoderm and F9 embryonal carcinoma cells in which mutant Endo B protein was constitutively expressed. By immunolocalization techniques a perturbation of the keratin network was revealed as well as concomitant disruption of vimentin IFs and displacement of surface desmosomal proteins, demonstrating an intimate structural association of Endo B/A filaments with these cellular components. In aggregates of differentiating F9 cells displaying altered Endo A/B IFs, the formation of a compact, polarized visceral endoderm layer was significantly compromised. These results indicate that an intact keratin network influences the three-dimensional formation of cell-cell or cell-substratum contacts in embryonic visceral endoderm.