How Is a Living Organism Assembled?

June 3, 2010 — -- 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."