Publication highlights

Researchers at the Crick have produced a new embryo model that self-organises around ten somites alongside a single neural tube, mirroring aspects of human embryos at 28 to 35 days after fertilisation. As the models don't contain a notochord, the team introduced signals that would have originally come from a notochord, and observed a shift in cell fates. They also saw spontaneous patterning in the neurla tube, showing it was developing into different identieis depending on the cell's location. This suggested that the somites and the neural tube were in close communication. The team confirmed that increased retinoic acid signalling in specific somite regions was likely due to signalling to the neural tube, allowing spontaneous patterning. This crosstalk helps prompt regional identities and may be important for later maturation to neuronal or skeletal tissues.

Thanks to continuous advances in human stem cell research, studies using embryo models are progressing quickly, including research happening at the Crick. Embryo models offer a scientific and ethical addition to the use of embryos from fertilised human eggs in research, but ethical guidelines sometimes have to play catch-up with scientific progress.

The challenge is to know how we would decide when an embryo model is ‘similar enough’ to an embryo as to fall under the same restrictions, since research keeps pushing the technology forward.

Naomi Moris, Group Leader of the Developmental Models Laboratory at the Crick, worked with an international group of biologists and ethicists to propose a refined definition of the human embryo, as a group of cells which have the potential to form a fetus, focusing on what the embryo can become rather than its origin. The group identified ‘tipping points’, where embryo models would stray into the territory of an embryo.

The cells that will eventually give rise to germ cells, sperm and egg, are originally made by the embryo early on in its development. These cells, called Primordial Germ Cells or PGCs, are an exciting group of cells to study because we still know relatively little about how they are first generated, how they move around the early embryo, and how they start to mature and eventually produce sperm or egg cells. However, current technology to make PGCs in the laboratory uses large, disorganised culture systems alongside specific chemicals to 'bias' the cells towards becoming PGCs. Instead of doing this, we have shown that mouse stem cells can be cultured in a controlled, 3D system that mirrors certain elements of the early mouse embryo.

In this work, the researchers show that these structures, called 'gastruloids', also contain PGCs, and that these cells not only appear in these structures, but that they interact with the other cells in the gastruloid in a manner that is very similar to the way they develop in the actual embryo. They also show that the gastruloid PGCs reach a more mature stage of development (at about the stage of a 13-15 days old mouse embryo) compared to traditional culture methods (that only reach day 9-10). This shows that not only can we make PGCs in a new way that might reveal new insights about these specific cells, but it also highlights the value of embryo-like models, including gastruloids, to generate rare cell types that might otherwise be difficult to access.