Mouse stem cells can self-organize into headless ‘little bananas’
Building a baby animal from just a few cells nestled in the mother’s uterus is complicated. But it turns out that a disorganized clump of cells in a dish can, with very little instruction, carry out some of that process on their own. A new study suggests such gastruloids—oblong 3D structures made from balls of cells derived from a mouse embryo—may give scientists a new way to study embryonic development in a lab dish.
Scientists reported in 2014 that clusters of about 300 mouse embryonic stem cells would self-organize into an elongated shape when kept in a growth-promoting broth and exposed to a compound that activates a key developmental gene called Wnt. In the new work, led by the same researchers, developmental biologist Alfonso Martinez Arias of the University of Cambridge in the United Kingdom and his collaborators describe how different types of cells developing in these gastruloids organize themselves much like an embryo, along the axes that eventually divide the body into front and back, top and bottom, and left and right.
“They make a little banana or a little zucchini,” says Denis Duboule, a geneticist at the University of Geneva and the Swiss Federal Institute of Technology in Lausanne, Switzerland, a co-author on the new paper. “You would expect to get sort of a mess, sort of a tumor, but no—you get something that is very highly organized.” And when the researchers analyzed the genes expressed over time by different cells in these tiny gastruloids, they found the pattern was remarkably similar to that of a mouse embryo, they reported yesterday in Nature.
Gastruloids are a far cry from an embryo, though. Perhaps the most salient difference: They don’t develop heads. But because it’s easy to make them in large numbers, they might give scientists a new model to study the sequence of genetic changes responsible for early embryonic growth.
For now, Duboule is using them to study the developmental effects of multiple genetic mutations that are hard to make simultaneously in mice, even with modern gene-editing technologies. He’s most interested in testing the effect of different mutations in a family of genes called Hox, whose precisely timed activation determines how different types of vertebrae form in the spine.
It’s yet to be seen whether the same approach will create useful models from human cells—which could reveal which steps in that elaborate genetic recipe are unique to our species, and how genetic defects might send it off the rails.