Mammalian embryos undergo dramatic shape changes upon implantation, and the cellular and molecular mechanisms underlying this transition were previously largely unknown. We have shown that this transition is directed by cross-talk between the embryonic and extra-embryonic tissues present at that time. We identified signalling pathways responsible for specific fate acquisition, which are required for embryo body and placenta formation in future development.
After the initial step of embryo remodelling during implantation, the embryo breaks symmetry for the first time in its life to define the future anterior and posterior parts of its body. This critical event is required for establishing the correct body plan. We have defined the function of the cells migrating to one side of the embryo during the peri-implantation period that break the embryo’s symmetry and have detailed distinct events, signalling pathways and molecules that are responsible for the correct progression of this process. We have also identified critical changes in the embryonic and extraembryonic parts of the embryo that contribute to the coordination of embryo growth and morphogenesis upon implantation and in early post-implantation development, after the anterior and posterior parts of the embryo are established. We have also shown that distinct adhesion molecules are required for embryo implantation and development, and that modulating their function may lead to unsuccessful implantation and death of the embryo.
Taken together, our above studies provide an in depth characterization of the cellular and molecular mechanisms underlying the transition from the pre- to post-implantation state, which were previously largely unknown. We have shown the significance of cross-talk between the embryonic and extra-embryonic tissues in the regulation and progression of development and future morphogenetic transitions.
An aberrant number of chromosomes in cells may result in cell death or congenital defects, and such cells need to be eliminated during early embryonic development. Using a mouse model, we have shown how cells having an aberrant number of chromosomes are preferentially eliminated from the lineage forming the future embryo body. Moreover, we have shown that healthy cells undertake compensatory divisions during the implantation stages to confer embryonic viability and described self-regulatory mechanisms to ensure its proper size and number of cells. Our results indicate how different processes work together to eliminate cells with genetic instabilities from the lineage forming the embryo body in development and to refine the embryonic cell population, ensuring that only “chromosomally fit” cells proceed through the development of the foetus.
The above findings demonstrate the highly specific regulative mechanisms of early development in mouse embryos, ensuring correct cell number and health during the implantation process and in the formation of embryonic and extra-embryonic structures. This knowledge has potential implications for human development and clinical application.
We have developed a new methodological approach to generate post-implantation mouse embryo-like structures from a mix of stem cells, representing cells present in the preimplantation embryo. Our results demonstrate that these structures can develop in a similar way to natural embryos, forming precursors of the entire brain, a beating heart, and a gut. They are also morphologically similar to natural embryos and form both embryonic and extraembryonic structures, just as is the case in natural mouse embryo development. Therefore, for the first time, we have developed a stem cell-based system that captures mouse embryogenesis in its entirety. In the future, these systems could significantly reduce the use of animals in research. We have already successfully used these systems to address distinct scientific questions about the roles of specific genes in developmental processes.
We have also attempted to translate the stem cell-derived embryo system from mouse to human by modelling early human embryo development with stem cells. However, we have shown that further improvement and research are needed to develop similar model that is as accurate as the mouse model.
