Forces driving cell sorting in the amphibian embryo

• Adhesion differences are the main driver of cell sorting, boundary formation and tissue positioning.
• Adhesion strength differences are not essential for sorting-related processes in the amphibian embryo.
• Tissue positioning in the amphibian embryo depends most likely on specific cell adhesion.
• Ectoderm-mesoderm boundary formation in the amphibian embryo depends on contact-induced cell repulsion.

Adhesion differences are the main driver of cell sorting and related processes such as boundary formation or tissue positioning. In the early amphibian embryo, graded variations in cadherin density and localized expression of adhesion-modulating factors are associated with regional differences in adhesive properties including overall adhesion strength. The role of these differences in embryonic boundary formation has not been studied extensively, but available evidence suggests that adhesion strength differentials are not essential. On the other hand, the inside-out positioning of the germ layers is correlated with adhesion strength, although the biological significance of this effect is unclear. By contrast, the positioning of dorsal mesoderm tissues along the anterior-posterior body axis is essential for axis elongation, but the underlying sorting mechanism is not correlated with adhesion strength, and may rely on specific cell adhesion. Formation of the ectoderm-mesoderm boundary is the best understood sorting related process in the frog embryo. It relies on contact-induced cell repulsion at the tissue interface, driven by Eph-ephrin signaling and paraxial protocadherin-dependent self/non-self recognition.