Let’s talk about gastrulation. For those unfamiliar with the term, it’s not as disgusting as it sounds. Gastrulation is a process in early embryonic development which leads to the generation of the three germ-layer tissues- ectoderm, endoderm, and mesoderm- from which all other tissue-types in the body are erived. 

The early (amniote) embryo coverts from a bilaminar structure of epithelial tissue plus and extra-embryonic layer, to a trilamiarone. A second function of gastrulation is that it defines the anterior-posterior body axis for the first time. In other words, it begins to distinguish the head end of the embryo from the tail end- this is pretty important if you want all your bits and pieces in the right place later on! 

One goal of scientists studying such processes is to generate a model of gastrulation using embryonic stem cells. Tantalizingly, this might be the first step to in vitro embryogenesis. In other words, if scientists crack this, they might be able to build a whole organism from stem cells....I won't debate whether this is a good thing or not.

What’s really remarkable about this process is that in vivo, it involves coordinated cell movement and ingression of cells out of the epithelium en masse, but only in a restricted area of the epiblast (a region termed the primitive streak in amniotes). Cells in the primitive streak undergo and epithelial-to-mesechymal transition (EMT) allowing them to leave the epithelium and migrate away. 

This raises many questions for developmental biologists. How do the migrating cells know when and where to migrate? How does the primitive streak form? How does it form in the right place? Keep in mind that all this is occurring while the embryo is growing!

Credit: University of Cambridge

One way to unlock the secrets of gastrulation would be to generate an in vitro model. That is, induce an anterior-posterior axis in an aggregate of embryonic stem-cells, then induce a primitive-streak-like region in the aggregate, to recapitulate germ-layer formation.

A big ask, no? Well, the above video caught my eye...take a look.

Here we see that expression of an endoderm marker (Sox-17-GFP) appears to become polarised to one side of the aggregate as it grows. It also becomes to become more elongated! We can conclude that this ball of cells has spontaneously broken symmetry- the cells at it's anterior end are different from those at its posterior. Plus, it has generate endoderm tissue!

Does this mean the aggregate is undergoing gastrulation in vitro?

Sadly, I would argue not. For me, the hallmarks of gastrulation are in the way it occurs- not the end products (AP axis, and the germ layer tissues). In vivo, gastrulation is a dynamic process, yet I see no evidence of cellular ingression and EMT here.

So while this is interesting, it is still a case of directed differentiation of embryonic stem cells, as opposed to 'gastrulation' in a test tube. 

While symmetry breaking similar to this may be the first step, we are still a long way from understanding the mechanisms through which which the body plan arises during development, and working out how to recapitulate this in vitro is still an enormous challenge.

That's what is great about science- there's still so much more to learn! I urge you to check out the paper related to this video, and make your mind up for yourself.

Front page image source:  College of The Atlantic. Original: McGraw-Hill