Self-organization from organs to embryoids by activin in early amphibian development.

Abstract

Embryonic development is a complex self-organizing process orchestrated by a series of regulatory events at the molecular and cellular levels, resulting in the formation of a fully functional organism. This review focuses on activin protein as a mesoderm-inducing factor and the self-organizing properties it confers. Activin has been detected in both unfertilized eggs and embryos, suggesting its involvement in early developmental processes. To explore its effects, animal cap cells-pluripotent cells from the animal pole of amphibian blastula-stage embryos-were treated with varying concentrations of activin. The results showed that activin induced mesodermal tissues, including blood, muscle, and notochord, in a dose-dependent manner. Co-treatment with activin and retinoic acid further promoted the development of kidney and pancreatic tissues, while activin alone stimulated the formation of beating cardiac tissue. In subsequent experiments, high concentrations of activin conferred an organizer-like activity on animal cap cells. The pretreatment duration affected outcomes: longer exposure induced anterior structures, such as eyes, while shorter exposure resulted in posterior structures, like tails. These findings reflect moderate self-assembly, where cells become increasingly organized. In another experiment, activin was used to create an artificial gradient. Explants cultured on this gradient developed into embryoids with well-defined anteroposterior, dorsoventral, and left-right axes, exemplifying higher-order self-organization. These results demonstrate that controlled activin gradients can drive the formation of nearly complete tadpole-like larvae, effectively recapitulating the processes of early embryogenesis. This system offers valuable insights into the mechanisms underlying axis formation and organogenesis, providing a promising platform for future research in developmental biology.