Self-renewal, proliferation and differentiation of tissue-specific stem cells and progenitors are governed by several critical developmental signaling pathways, including the Hedgehog, Hippo and Wnt pathways. Dysregulation of these pathways leads to formation of a broad range of human cancers, including cancers arising from the gastrointestinal tract. The Mao laboratory uses a combination of cellular and mouse genetic approaches to understand the mechanism underlying these pathways in regulation of stem/progenitor cell function, tissue patterning, and their involvement in gastrointestinal tumorigenesis.