During early embryonic development, cellular interactions coordinate the transformation of a small, uniform cluster of cells into a complex three-dimensional multicellular organism. Errors during early embryonic development can result in developmental abnormalities, but it is largely unknown how and when such abnormalities arise. A majority of studies investigating the mechanisms underlying embryonic development rely on animal models, such as mice. However, it is technically challenging to maintain and image mouse embryos in long-term cultures. Additionally, the generation of genetically modified embryos is time-consuming and inefficient, and mouse embryos cannot be easily obtained in large numbers, limiting their use in large-scale genetic or drug screening procedures.
The discovery that mouse embryonic stem (ES) cells derived from mouse embryos can be propagated in a pluripotent state in vitro circumvented some of the abovementioned challenges, allowing scientists to study the processes that regulate embryonic development in vitro at a larger scale. Following this discovery, early two-dimensional (2D) and three-dimensional (3D) ES cell culture systems were developed, but they did not accurately capture the complex 3D morphology of the embryo. Therefore, these culture systems could not be used to understand, among other topics, the 3D interactions between the embryonic and extra-embryonic lineages, coordinated 3D cellular morphogenetic rearrangements (associated with embryonic processes such as gastrulation), or processes that ensure the appearance of embryonic organs in the correct position along the embryo's body axes.
To overcome these obstacles, Susanne van den Brink and her colleagues at the van Oudenaarden lab (Hubrecht Institute, Netherlands) recently developed a mouse ES cell-based protocol with which 3D embryo-like organoid structures can be generated. These structures (termed gastruloids) recapitulate many of the key events of mouse embryonic post-implantation development, including germ layer and body axis formation (van den Brink et al. 2014; Turner et al. 2017; Beccari et al. 2018; van den Brink et al. 2020). To generate these structures, the scientists used Takara Bio's NDiff 277 medium to efficiently and reproducibly differentiate mouse ES cell aggregates towards an early embryonic state. Upon subsequent application of a Wnt agonist, these aggregates elongate, resulting in the formation of a structure containing most embryonic cell types present in the correct location along the anterior-posterior (head-tail) body axis. As these processes normally take place during the embryonic development phase known as gastrulation, these embryo-like organoid structures are termed gastruloids, and they can be used to study mouse embryonic development in vitro in a high-throughput manner.