Scientists are a step closer to unraveling one of the greatest mysteries of the biological world: how stem cells morph into different organs and tissues to create a living creature.
Thanks to a remarkable little fish, and some very cleaver engineering at Lawrence Berkeley National Laboratory, they now can watch in real time as an undistinguishable blob of cells gradually change into an embryonic zebra fish, one cell at a time.
Until now, scientists could only observe this process by harvesting a living animal and examining each step as it moves through the embryonic stage.
It would be far more constructive if they could actually see those changes from the very beginning in a live subject and follow the process through to the end. And that's exactly what researchers in Carolyn Bertozzi's lab have accomplished.
The star of their show, however, is a tiny transparent fish that has become a lab darling. Scientists can literally see inside a zebra fish without having to kill it and cut it up.
Bertozzi's team wasn't interested in just looking inside the fish. They wanted to examine it on the cellular level with an atomic force microscope. The researchers invented a way to zero in on sugar molecules, called glycans, on the surface of individual cells inside a zebra fish within seven hours after her eggs were fertilized.
"We wanted to look at how the sugars change in a live embryo all the way from the point of conception to when the organism is fully developed with all its organs and systems, so we did that with the zebra fish," Bertozzi said in a telephone interview.
Initially, the embryo "just looks like a ball of cells and there's no obvious formation of organs yet," Bertozzi said. "So a lot of these cells have not yet made a decision about what they are going to be when they grow up. We want to look at the sugars as they make those decisions."
What role could sugar possibly play in this complex process? A huge role, according to Bertozzi, who started studying glycans a couple of decades ago because nobody knew much about them. As she put it, the field was "uncharted territory."
After many years of research in her lab and other labs around the world, sugars are earning a lot of respect.
Bertozzi believes they might be the on-scene commander, and the traffic cop, and the communications director in the complex process of assembling a living animal. Do they play a major role in the process by which stem cells morph into different cells?
"I'd be shocked if they didn't," she said.
Glycans, or sugar molecules, are found primarily on the outer surface of all cells.
"The description I use for my students [at U.C. Berkeley] is it's like a peanut M&M: It's got a sugar coating, but the sugars look like they encode a language," Bertozzi said. "So when two cells get together, they kind of peck on each other's sugars to get information."
So sugars probably act as architects and traffic cops, directing some stem cells to become neurons, and others to become blood cells, and so on throughout the formation of the embryo.
But not only do the stem cells morph, so do the sugars on their surface. The sugars are chemically and biologically different on a stem than on an adult cell. It's not clear why that should be the case, but it may turn out to be very helpful a few years, or possibly decades, down the road.