Cells migrating over long distances, such as primordial germ cells (PGCs), which migrate through the developing embryo, encounter different cell and tissue types on their journey. Although it is known that cells alter their protrusion type and migration mode in different 2D and 3D substrates in vitro, how this translates in vivo has been less well described. Now, Lukasz Truszkowski, Erez Raz and colleagues examine PGC migration within different substrates by creating single germ-layer zebrafish embryos. They discover that while migration speed and track straightness is similar for PGCs migrating in ectoderm or mesoderm, the bleb frequency and bleb size is reduced in PGCs moving through ectoderm. They identify that the difference in cortical tension between the two germ layers is likely to be a key factor driving the alteration in bleb dynamics. The authors find that PGCs displaying lower bleb frequency and size form more actin-rich protrusions, indicating that the cells adopt a different protrusion type when migrating in ectoderm. This shift is correlated with a slightly elevated RhoA activity and more evenly distributed cortical ezrin. Together, these data demonstrate that PGCs change their migration mode upon contact with different substrates and may have broad implications for studying other cell types, including cancer cells.