Controlling where and when forces are generated during tissue morphogenesis
Professor Karen Kasza, Columbia University
Mechanical forces generated by cells drive changes in tissue shape and structure that are essential to building functional tissues and organs during embryonic development. One of the primary force-generating machines inside cells is the contractile actomyosin network, an assembly of myosin II motor proteins and actin filament biopolymers. Mechanical forces generated by actomyosin are likely to have multiple roles in development: driving cell movements and cell shape changes, tuning tissue mechanical properties, and influencing biochemical processes that control cell behavior. Yet, due to the strong coupling between mechanical and biochemical factors during morphogenesis and the lack of experimental tools for manipulating mechanical forces in vivo, it has remained an experimental challenge to dissect the roles of mechanical forces during morphogenesis. To address this, my lab is combining live imaging and genetics with emerging technologies for manipulating forces inside cells to study the mechanics of morphogenesis in the model organism Drosophila melanogaster. We have developed a collection of optogenetic tools that provide light-gated, genetically encoded control over cell-generated contractile forces to manipulate epithelial tissues during morphogenetic movements at various stages in Drosophila development. We are investigating how mechanical forces influence epithelial tissue shape, structure, mechanics, and remodeling during morphogenesis. Together, these studies shed light not only on how mechanical forces shape tissues during normal development but also on how mechanical factors might contribute to improper tissue movements associated with birth defects in humans.