Mouse embryonic submandibular gland epithelium loses its tissue integrity during early branching morphogenesis.

During the development of the mouse submandibular gland, the epithelium undergoes not only shape changes to produce extensively branched lobules and stalk, but also changes in cell arrangement from a cell mass to a cavitated cell sheet. The present study examined the organization in the developing epithelium of intercellular adhesion systems and of actin-containing microfilaments. E-cadherin and beta-catenin, which are components of cell-to-cell adherens junctions in epithelial cells, were distributed along the cell periphery of almost the entire epithelium of the submandibular gland at all stages examined and were mainly localized at the apical region of the oral epithelium. Actin-containing microfilaments, which are associated with cell-to-cell adherens junctions, showed a distribution similar to that of those molecules. In contrast, although the distributions of desmoplakins I/II, major desmosomal proteins, and ZO-1 (a tight junction protein) were seen in the oral epithelium and proximal stalk of the submandibular gland epithelium, signals representing these molecules were absent from or much reduced in the submandibular gland epithelium of the cell mass at the 12- and 13-day stages. In the 14-day gland, they strongly appeared in the cells facing the appearing lumens, whereas they were weakly scattered within the terminal lobules that were still a part of the cell mass. These findings suggest that cell-to-cell adhesion systems are differentially regulated during the epithelial morphogenesis of the submandibular gland and that the integrity of the submandibular gland epithelium is lost during the early stages of development, indicating the tissue to be a rather plastic structure.