A role for Rho GTPases and cell-cell adhesion in single-cell motility in vivo

Cell migration is central to embryonic development, homeostasis and disease(1), processes in which cells move as part of a group or individually. Whereas the mechanisms controlling single-cell migration in vitro are relatively well understood(2-4), less is known about the mechanisms promoting the motility of individual cells in vivo. In particular, it is not clear how cells that form blebs in their migration use those protrusions to bring about movement in the context of the three-dimensional cellular environment(5,6). Here we show that the motility of chemokine-guided germ cells within the zebrafish embryo requires the function of the small Rho GTPases Rac1 and RhoA, as well as E-cadherin-mediated cell-cell adhesion. Using fluorescence resonance energy transfer we demonstrate that Rac1 and RhoA are activated in the cell front. At this location, Rac1 is responsible for the formation of actin-rich structures, and RhoA promotes retrograde actin flow. We propose that these actin-rich structures undergoing retrograde flow are essential for the generation of E-cadherin-mediated traction forces between the germ cells and the surrounding tissue and are therefore crucial for cell motility in vivo.