One of the fundamental processes of morphogenesis is dome formation, but many parts of the mechanisms has been unexplored. Previous in vitro studies showed that osmotic gradient is the driving factor of the dome formation. However, these investigations were performed without extracellular matrix (ECM), which provides structural support to morphogenesis. With the use of ECM, we observed that basal hypertonic stress induced stable domes in vitro that have not been seen in previous studies. These domes developed from the ECM swelling via aquaporin water transport activity. Based on computer simulation, uneven swelling, with a positive feedback between extending cell and enhanced water transport, was a cause for dome formation. These results indicate that osmotic gradient induces dome morphogenesis via both enhanced water transport activity and subsequent ECM swelling.