Cell migration requires a dramatic and coordinated reorganization of the different elements of the cytoplasmic cytoskeleton, composed of three types of filamentous structures: actin microfilaments, microtubules and intermediate filaments. Mesenchymal cells strongly interact with and exert traction forces on the extracellular matrix through integrin-based focal adhesions to move forward. The actin polymerization contributes to membrane protrusion while the acto- myosin network forming stress fibers generate the traction forces. Microtubules have been shown to play a key role in cell front-to-rear polarization as well as in the control of focal adhesion dynamics and distribution and in focal adhesion associated stress fibers. Finally, intermediate filaments are thought to contribute their mechanical properties to cell migration. Looking at the collective directed migration of primary astrocytes in vitro, we have been investigating how these three cytoskeletal structures influence one another to perform coordinated tasks such as nucleokinesis, focal adhesion turnover, mechanotransduction and cell- cell adhesions and insure the collective behavior of the cell monolayer.