Developmental patterning of the circumvallate papilla.

Organogenesis is regulated by the sequential and reciprocal interactions between epithelial and mesenchymal tissues. Many molecules, including growth factors, transcription factors, extracellular matrices, cell surface receptors, and matrix degrading enzymes, have been found to be involved in this process. To investigate the molecular mechanism responsible for morphogenesis of the circumvallate papilla/von Ebners' gland complex, we examined the expression patterns of selected cell adhesion molecules, extracellular matrix molecules, innervation and cell division in the circumvallate papilla of mouse embryos from embryonic day 11.5 (E11.5) to E14. At E11.5-E13.5, the lingual epithelium, the site where the circumvallate papilla will develop, is negative for BrdU labeling. At E14-E15, we detected cell division in the papillary area, especially in the epithelial invagination where von Ebners' minor salivary gland will form. The basement membrane component, laminin, is expressed as a continuous thin line separating the epithelia from the underlying mesenchyme, but it is broadly and strongly expressed in the area wherethe nervefibers penetrate into the circumvallate papilla. At the E12-E12.5 stage of development, the epithelial thickening shows intense E-cadherin staining in the superficial and basal layers, but weak E-cadherin staining in the suprabasal layer. E-cadherin is strongly expressed, but appears dispersed among the basal layer of lingual epithelium, the site where nerve fibers will innervate. At E13, nerve fibers reach the circumvallate papilla. These nerve fibers penetrate into and split the epithelial cell mass into two stalks which will later differentiate to form the von Ebners' gland. These results suggest that 1) the formation of the circumvallate papilla does not initially depend on cell division, 2) cell migration likely plays a major role during circumvallate placode formation, 3) E-cadherin and laminin may play a role in nerve guidance and 4) innervation impacts the final morphogenesis of the circumvallate papilla.