A key question in developmental and stem cell biology is to understand how tissue morphogenesis and regeneration are regulated through the interplay between cells and their surrounding environment. The mouse tooth provides an excellent model to study the mechanism by which cell-cell and cell-matrix interactions determine tissue shapes, patterning, and stem cell-based renewal. YAP and TAZ are transcriptional co-factors in the Hippo signaling pathway and play a pivotal role in relating micro environmental signals to control cell proliferation and differentiation. Using this model, we have found that YAP/TAZ are regulated by a novel integrin/CDC42 pathway and function to initiate and maintain the high-proliferation state in the transit-amplifying cells. This is in contrast to the low-proliferating resident dental stem cells, which we believe to be regulated by cell density-driven compression forces that is modulated through proliferation and cell adhesion. I will therefore explore these possibilities and ways we could employ to test these ideas.