Powering morphogenesis: multiscale challenges at the interface of cell adhesion and the cytoskeleton

Among the defining features of the animal kingdom is the ability of cells to change shape and move. This underlies embryonic and postembryonic development, tissue homeostasis, regeneration, and wound healing. Cell shape change and motility require linkage of the cell's force-generating machinery to the plasma membrane at cell-cell and cell-extracellular matrix junctions. Connections of the actomyosin cytoskeleton to cell-cell adherens junctions need to be both resilient and dynamic, preventing tissue disruption during the dramatic events of embryonic morphogenesis. In the past decade, new insights radically altered the earlier simple paradigm that suggested simple linear linkage via the cadherin-catenin complex as the molecular mechanism of junction-cytoskeleton interaction. In this Perspective we provide a brief overview of our current state of knowledge and then focus on selected examples highlighting what we view as the major unanswered questions in our field and the approaches that offer exciting new insights at multiple scales from atomic structure to tissue mechanics.