AbstractCell adhesion must be precisely regulated to enable both dynamic morphogenetic processes and the subsequent transition to stable tissue maintenance. Integrins link the intracellular cytoskeleton and extracellular matrix, relaying bidirectional signals across the plasma membrane. In vitro studies have demonstrated that multiple mechanisms control integrin‐mediated adhesion; however, their roles during development are poorly understood. We used mutations that activate or deactivate specific functions of vertebrate β‐integrins in vitro to investigate how perturbing Drosophila βPS‐integrin regulation in developing embryos regulation affects tissue morphogenesis and maintenance. We found that morphogenetic processes use various β‐integrin regulatory mechanisms to differing degrees and that conformational changes associated with outside‐in activation are essential for developmental integrin functions. Long‐term adhesion is also sensitive to integrin dysregulation, suggesting integrins must be continuously regulated to support stable tissue maintenance. Altogether, in vivo phenotypic analyses allowed us to identify the importance of various β‐integrin regulatory mechanisms during different morphogenetic processes. Developmental Dynamics 240:36–51, 2011. © 2010 Wiley‐Liss, Inc.