Developmental Plasticity Is Bound by Pluripotency and the Fgf and Wnt Signaling Pathways

Summary

Plasticity is a well-known feature of mammalian development, and yet very little is known about its underlying mechanism. Here, we establish a model system to examine the extent and limitations of developmental plasticity in living mouse embryos. We show that halved embryos follow the same strict clock of developmental transitions as intact embryos, but their potential is not equal. We have determined that unless a minimum of four pluripotent cells is established before implantation, development will arrest. This failure can be rescued by modulating Fgf and Wnt signaling to enhance pluripotent cell number, allowing the generation of monozygotic twins, which is an otherwise rare phenomenon. Knowledge of the minimum pluripotent-cell number required for development to birth, as well as the different potentials of blastomeres, allowed us to establish a protocol for splitting an embryo into one part that develops to adulthood and another that provides embryonic stem cells for that individual.

Abstract

Graphical Abstract

Highlights

► Half embryos follow the same clock as intact embryos, but their potential is not equal ► To support development, four pluripotent cells must be generated before implantation ► Fgf/Wnt signal modulation enhances pluripotency to rescue half-embryo development ► ESCs and a viable mouse can be derived from a single embryo with high efficiency

Abstract

It is a well-known feature of early mouse development that healthy mice can form from embryos split into two parts. How the mouse achieves this remarkable feat is unknown; thus, Morris, Guo, and Zernicka-Goetz examined this phenomenon by filming halved embryos as they developed. They found that some half embryos do not make enough pluripotent cells to support development, but this deficiency can be rescued by modulating Fgf and Wnt signaling. Using this rescue, the authors were able to derive embryonic stem cells without compromising embryo viability.