The effects of chlorcyclizine-induced glycosaminoglycan alterations on palatal mesenchyme-basal lamina relationships in the mouse

Abstract

The relationships of mesenchymal cells to the basal lamina underlying regions of the palatal-shelf epithelium that are known to increase in cell density during shelf reorientation are quantitatively different from those of cells underlying neighboring regions that do not increase in cell density. Chlorcyclizine-induced alterations of the extracellular matrix were used to investigate the possible contribution of extracellular matrix to these differences. Chlorcyclizine causes hyaluronate and the chondroitin sulfates to be degraded into pieces with smaller molecular weights and lower charge densities, with little or no effect on their synthesis, and also results in cleft palate. Pregnant CD-1 mice were gavaged with chlorcylizine on days 10.5, 11.5, and 12.5 of gestation, and the fetuses were harvested on day 13.5. Some palatal shelves were excised immediately and fixed for electron microscopy; other heads were partially dissected and incubated for 4 hr prior to fixation. In normal heads differences in mesenchymal cell configurations are detectable after 4 hr in vitro . Electron micrographs were taken of the epithelial-mesenchymal interface in nasal and oral regions that increased in epithelial cell density and in nasal and oral regions which did not. Several variables of mesenchymal cell configuration were measured in a 500-nm-wide zone delimited on photographic prints. Chlorcyclizine-induced glycosaminoglycan alterations resulted in quantifiable, region-specific differences in mesenchymal cell relationships to the basal lamina and in the ultrastructural appearance of the zone immediately subjacent to the basal lamina. These results suggest that the epithelial-mesenchymal interface and sublaminar zone of the nasal and oral regions as well as their active and inactive segments may be constitutively different.