Zebrafish have emerged as a powerful genetic model system for identifying and mapping signaling pathways critical to embryological development. Since the zebrafish gastrointestinal tract displays many features similar to that of higher vertebrates, we utilize zebrafish as a model system to study the role of APC, retinoic acid, and DNA methylation in directing development and differentiation of the gastrointestinal tract. For example, using this system we have recently confirmed a genetic relationship between APC and retinoic acid in controlling zebrafish gut development and differentiation. Our data show that knock down of either APC or retinoic acid biosynthesis in zebrafish results in the development of intestines that lack differentiated epithelial cells. Treatment of either APC mutant embryos with retinoic acid rescued the defective phenotypes, thus placing retinoic acid downstream of the APC tumor suppressor.