STUDIES OF INTESTINAL STEM-CELLS USING NORMAL, CHIMERIC, AND TRANSGENIC MICE

The mouse intestinal epithelium represents a continuous developmental system. Its four principal differentiated cell types-enterocytes, goblet, enteroendocrine, and Paneth cells-are derived from a common multipotent stem cell located near the base of monoclonal crypts. Members of these four lineages undergo rapid and perpetual renewal along an anatomically well-defined pathway. The gut epithelium provides a unique mammalian model for studying the biological features of stem cells (e.g., their ability to undergo asymmetric division, their enormous proliferative potential, their capacity for functional anchorage in a niche), examining how stem cell hierarchies are established and maintained in renewing cell populations, analyzing the relationships between passage through the cell cycle and lineage allocation (commitment), and defining the mechanisms that give stem cells a "positional address" along the cephalocaudal axis, allowing them to generate regional differences in the differentiation programs of their derived lineages (axial pattern formation).