THE DIFFERENTIATION AND LINEAGE DEVELOPMENT OF GOBLET CELLS IN THE MURINE SMALL-INTESTINAL CRYPT - EXPERIMENTAL AND MODELING STUDIES

The objective of this study was to provide a new insight into the orig in and lineage development of mucus-producing cells in the small intes tinal crypt. For this, new experimental data were obtained from both c rypt sections and whole mounts. Model simulation studies were undertak en to investigate which rules are most likely to govern the dynamic ce llular development and goblet cell pedigree. We have measured the freq uency of mucus-secreting goblet cells (using alcian blue and periodic acid Schiff's stains) at each cell position in the ileal murine crypt. These measurements, made on sections, overestimate the number of gobl et cells because of the size and centripetal position of the stained c ytoplasm. The correction factor for this overscoring has been measured to be 0.25 by two independent methods. The data suggest that there ar e about 12 functional goblet cells per crypt many of which retain an a bility to divide. We have also determined the labelling index of the c rypt goblet cells at each cell position. Spatially, goblet cells exhib it a small degree of clustering in the crypt and show a good mixture w ith columnar cells. We have adapted our earlier dynamic matrix-based c omputer simulation model to take into account goblet cell differentiat ion. The modelling suggested the following conclusions: firstly, goble t cells do not have their own stem cells but share a common stem cell with the columnar cells; secondly, the goblet lineage differentiates f rom the transit population two to three generations before the end of the lineage; and thirdly, the decision to switch on goblet properties is stochastic at a specific step in the development of columnar cells.