AbstractDuring embryonic development, cells must navigate through diverse three-dimensional environments robustly and reproducibly. The zebrafish posterior lateral line primordium (PLLp), a group of approximately 120 cells which migrates from the otic vesicle to the tip of the tail, spearheading the development of the lateral line sensory system, is an excellent model to study such collective migration in an in vivo context. This system migrates in a channel formed by the underlying horizontal myoseptum and somites, and the overlying skin. While cells in the leading part of the PLLp are flat and have a more mesenchymal morphology, cells in the trailing part progressively reorganize to form epithelial rosettes, called protoneuromasts. These epithelial cells extend basal cryptic lamellipodia in the direction of migration in response to both chemokine and FGF signals. In this study, we show that, in addition to these cryptic lamellipodia, the core epithelial cells are in fact surrounded by a population of motile cells which extend actin-rich migratory processes apposed to the overlying skin. These thin cells wrap around the protoneuromasts, forming a continuous sheath of cells around the apical and lateral surface of the PLLp. The processes extended by these cells are highly polarized in the direction of migration and this directionality, like that of the basal lamellipodia, is dependent on FGF signaling. Consistent with interactions of sheath cells with the overlying skin contributing to migration, removal of the skin stalls migration. However, this is accompanied by some surprising changes. There is a profound change in the morphology of the sheath cells, with directional superficial lamellipodia being replaced with the appearance of undirected blebs or ruffles. Furthermore, removal of the skin not only affects underlying lamellipodia, it simultaneously alters the morphology and behavior of the deeper basal cryptic lamellipodia, even though these cells do not directly contact the skin. Directional actin-rich protrusions on both the apical and basal surface and migration are completely and simultaneously restored upon regrowth of the skin over the PLLp. We suggest that this system utilizes a circumferential sheath of motile cells to allow the internal epithelial cells to migrate collectively in the confined space of the horizontal myopseptum and that elastic confinement provided by the overlying skin is essential for effective collective migratory behavior of primordium cells.
Zebrafish Posterior Lateral Line primordium migration requires interactions between a superficial sheath of motile cells and the skin
