Thanks to Glowing Proteins, Scientists Can Now See Embryos Develop Cell by Cell

The research can help scientists figure out what genes spur development.

Mar 19 2014, 5:25pm
An embryo with certain cells lit up. Image: Julius Barsi

We've learned a lot about evolution, medicine, and anatomy by watching species develop from being a zygote into a living, breathing organism. But simply grabbing a microscope to watch life develop isn't as precise as it could be. Now, thanks to a new technique developed at CalTech, scientists can literally light up individual cells within an embryo to watch them specialize, a move that could answer key questions about the role genetics play in an organism's development.

In an embryo, certain cells eventually specialize, becoming neurons, blood cells, skin cells, and all the other stuff that lets you survive on this crazy planet. But, until now, we’ve had no good way of isolating these cells to see how they develop within an embryo, leaving us to study organism development as a whole. 

Using artificial chromosomes and the principles of genetic engineering, the CalTech team has come up with a way to pull out individual cells to study them in a move that, in the near term, will help us understand each step of a species’ development, but could eventually lead to better ways of diagnosing disease.

To be sure, the technology is still in its infancy, and it’s going to take several years before we begin to see applications for it, but the basic research sounds promising. Julius Barsi, who is on the team that developed the method, calls it “bleeding edge tech,” and the team is really just getting started on this. He’s working on sea urchin embryos—an organism that’s ideal because it’s already pretty well-understood and isn’t nearly as complicated as, say, a mouse, which Barsi says he’ll begin working on next.

“When you look at development in a cell or tissue culture, you can often get a poor representation of what’s going on,” Barsi said. “But if you specifically pull out a single cell type from an embryo, you have a clever way of looking at a specific neuron to see why genes are expressed in one way or another.”

Right now, scientists have a couple ways of isolating cells, but, as Barsi explains in an upcoming paper in Genome Research, there’s no way to pick and choose which cells you want, and doing it from an embryo is even more problematic. 

“Although individual cell types of interest have been recovered by various methods and analyzed, systematic recovery of multiple cell type specific gene sets from whole developing organisms has remained problematic,” he writes.

Barsi says the goal is to create a “blueprint” that shows exactly how an organism goes from zygote to birth. Genetic markers can be put into certain cell types to see exactly what genes are causing a certain thing to happen, which obviously has major future implications for determining what genetic information is causing deformities or diseases to happen.

“Now you can connect the genes to a given function,” he said. “You can see what specifies a cell to become a certain cell, what enables a cell to do what it does, what tells it to secrete hormones, to become a neuron.”

In side A, you can see one specific cell lit up. Side B features disagreggated cells within an embryo. Image: Julius Barsi

Identifying and pulling a cell out of a living matrix is no easy task, and Barsi’s team had to get creative to solve it. To do it, they have to essentially genetically modify the embryo to light up certain cells. To make that happen, they’ve engineered “artificial chromosomes” that can be injected into the embryo, which are eventually incorporated into the organism’s DNA.

It’s the exact same process that’s used with any transgenic embryo—that is, any embryo that we know how to genetically modify. It’s the same way we grow human ears on the back of mice, make plants that glow in the dark, or genetically modify crops.

“We have it hooked up to what’s called a reporter, a green fluorescent protein, and we inject it into the fertilized egg. That is then incorporated through the embryo’s repair mechanisms, and it literally lights up,” he said. “You can do it with any cell type you desire.”

Because genetically modifying human embryos isn’t exactly kosher, Barsi says that the process won’t be used on humans, at least anytime soon. But a lot can be gleaned from a mouse or ape model, which is much more likely to happen. 

As I said earlier, we don’t know what the end result of this research is going to be, but at the very least, it’s going to let us learn a lot more about how organisms go from being a clump of cells to being fully formed.