The molecular mechanisms that integrate cellular polarity with tissue architecture during epithelial morphogenesis are poorly understood. Using a three-dimensional model of epithelial morphogenesis, Martin-Belmonte et al. (2007) report that the phosphatase PTEN and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] regulate the GTPase Cdc42 and the kinase aPKC to generate the apical plasma membrane domain and maintain apical-basolateral polarity.