Formation of the body axes is crucial for ensuring that body parts are correctly positioned during embryonic development. It was believed that the head-tail axis is primarily determined by the interplay between Nodal and BMP signals. However, a new study led by research groups at the Max Planck Institute of Molecular Physiology and the Max Planck Institute of Molecular Biomedicine has revealed an additional player in this system. In the absence of BMP, beta-catenin acts as a Nodal antagonist, providing a flexible solution for axis formation in embryos with different shapes.
The three body axes – head-tail, front-back, and right-left – are established early in embryonic development, dictating the orientation of body parts. The activation of regulatory genes along these axes leads to the development of specific cell types and tissues, ultimately determining the body’s blueprint. Despite the importance of body axes, many questions regarding axis formation remain unanswered, sparking further research in this field.
In mice, the head-tail axis is the oldest body axis and is established shortly after fertilization. The embryo at this stage resembles a cup with two cell layers and a thick lid. The anterior visceral endoderm (AVE) cell population forms at the bottom of the cup and plays a crucial role in axis formation. Prior studies suggested that the antagonism between Nodal and BMP signals controls this process, with Nodal signaling dominating at the cup’s bottom, where AVE cells differentiate.
The Max Planck researchers developed a novel embryo-like model system without a lid, consisting of epiblast and visceral endoderm (VE) cells. Despite the lack of BMP signaling from extraembryonic tissue, an AVE cell population was able to form from the VE cells, serving as the starting point for the first body axis development. Beta-catenin, a signaling molecule previously associated with another body axis, was found to be essential for this process. The distribution of BMP and other mechanisms may play a role in the formation of the first body axis in human embryos, which have a disc-like structure.
The success of the study was attributed to the use of two-layer embryo-like aggregates made up of cells from a single stem cell line. This ensured identical genetic backgrounds and communication systems among the cell populations, allowing them to be on the same wavelength during the research. The researchers believe that human embryonic stem cell aggregates based on this system could serve as a valuable tool for investigating events during embryonic development in the future, offering insights into axis formation and other key processes.