Wnt and BMP signalling direct anterior-posterior differentiation in aggregates of mouse embryonic stem cells.

Stem-cell-based embryo models have allowed greater insight into peri-implantation mammalian developmental events that are otherwise difficult to manipulate due to the inaccessibility of the early embryo. The rapid development of this field has resulted in the precise roles of frequently used supplements such as N2, B27 and Chiron in driving stem cell lineage commitment not being clearly defined. Here, we investigate the effects of these supplements on embryoid bodies to better understand their roles in stem cell differentiation. We show that Wnt signalling has a general posteriorising effect on stem cell aggregates and directs differentiation towards the mesoderm, as confirmed through the upregulation of posterior and mesodermal markers. N2 and B27 can mitigate these effects and upregulate the expression of anterior markers. To control the Wnt gradient and the subsequent anterior versus posterior fate, we make use of a BMP4 signalling centre and show that aggregates in these conditions express cephalic markers. These findings indicate that there is an intricate balance between various culture supplements and their ability to guide differentiation in stem cell embryo models.

Gastruloids: A Novel System for Disease Modelling and Drug Testing.

By virtue of its inaccessible nature, mammalian implantation stage development has remained one of the most enigmatic and hard to investigate periods of embryogenesis. Derived from pluripotent stem cells, gastruloids recapitulate key aspects of gastrula-stage embryos and have emerged as a powerful in vitro tool to study the architectural features of early post-implantation embryos. While the majority of the work in this emerging field has focused on the use of gastruloids to model embryogenesis, their tractable nature and suitability for high-throughput scaling, has presented an unprecedented opportunity to investigate both developmental and environmental aberrations to the embryo as they occur in vitro. This review summarises the recent developments in the use of gastruloids to model congenital anomalies, their usage in teratogenicity testing, and the current limitations of this emerging field.