The early embryo becomes a watertight cluster of cells, creating junctions between them that function like the stitches between panels of a soccer ball.
The process, discovered by A*STAR scientists, centers on a protein called actin, which fashions a thread-like network inside every cell of the body. In the early mouse embryo, actin additionally forms a ring-like structure on the outer surface of cells.
Similar actin rings, found in certain cells of the adult body, typically contract inward to aid in wound closure and cell division. However, the team found that in a crucial stage of early development, as the embryo matures from a slack 16-cell aggregate to a tight 32-cell ball, the actin rings expand outward toward the borders of neighboring cells, where they interlock and recruit other proteins to seal the embryo into its cohesive spherical form.
This helps to make the outermost cells watertight, an essential step in the proper development of the early embryo. Errors in this process “may lead to implantation failure, fetal defects and miscarriages,” says Jennifer Zenker, postdoctoral scientist at the A*STAR Institute of Molecular and Cell Biology and the first author of the new study.
“An advanced knowledge of the fundamental cellular and molecular mechanism controlling early development could further improve the application of assisted reproductive technologies, stem cell research and birth rates,” she adds.
Zenker works in the laboratory of developmental biologist Nicolas Plachta, who co-led the study together with Maté Biro, a biophysicist at the University of New South Wales in Australia.
The researchers used high-speed imaging techniques to observe the dynamics of the actin rings on the surface of 2.5-day-old mouse embryos. They labeled the actin filaments with fluorescent markers and watched as the expanded rings recruited other factors at the cell boundaries that stabilize the stretched loops.
The resulting tension then promoted the zipping of adjacent rings at cell junctions, thereby sealing the embryo from outside fluids. “This shows the importance of the crosstalk between the actin network and other types of filaments of the internal skeleton for its formation, organization and turnover,” Zenker says.
According to Zenker, research teams had previously failed to see this dynamic process because they looked only at fixed specimens at a single time point. “Our lab uses advanced imaging technologies to study the living mouse embryo,” she says. “This allows us to follow the real-time development of the mouse embryo in 3D at the frequency of minutes.”
The A*STAR-affiliated researchers contributing to this research are from the Institute of Molecular and Cell Biology. For more information about the team’s research, please visit the Plachta Lab webpage.