The mammalian intestinal epithelium represents a unique model system for studying cellular differentiation since it undergoes continuous and rapid renewal. Perpetual differentiation results in the generation of its four principal cell types, each with a unique phenotype. The processes of proliferation and cellular differentiation are topologically very well organized. Gradients in gene expression are established and maintained in several spatial dimensions within this epithelium. Recent experiments involving mouse aggregation chimeras and transgenic mice have provided insights about the origins of intestinal stem cells, the migration pathways followed during cellular differentiation as well as the molecular mechanisms which produce complex geographic differences in gut gene expression. The purpose of this mini-review is to emphasize the usefulness of these powerful methods for examining questions related to enteric epithelial biology.