The mouse gut epithelium represents a dynamic, geographically well organized, developmental system for examining self-renewal and differentiation. Reagents are now available for identifying the molecular mechanisms that regulate cell fate in the gut, the migration-associated differentiation programs of its component cell lineages, and its axial patterning. Considerable attention needs to be paid to two variables when studying gastrointestinal epithelial cell biology: space and time. This has necessitated the use of normal, chimeric, and transgenic animals as experimental models.