Sugars produced at different time points during zebrafish development were distinguished using multicoloured fluorescent reagents. Credit: Courtesy of Carolyn Bertozzi

To study proteins, scientists can quite easily hook the gene that encodes the protein of interest up to a gene for a fluorescent protein and then hunt out the coloured cells. But although sugars on cell surfaces can reveal much about the cells' activity, these sugars are much harder to visualize than proteins. Now, researchers led by Carolyn Bertozzi at the University of California, Berkeley, have found a way to make these sugars detectable within zebrafish embryos. Publishing this month in Science, the researchers show that this method can track distinct populations of cells during development. Jeremy Baskin, a member of the Bertozzi lab and an author of the paper, says the technique is being applied to other model systems and could be applied to study cell-fate decisions.

Bertozzi and colleagues used an unnatural sugar that cells can incorporate into larger sugars called glycans. Glycans are naturally found on cell surfaces and can reveal information about the state of cells' metabolism and secretory machinery. The unnatural sugar was also designed to react with fluorescent probes. The researchers introduced their sugar into developing zebrafish embryos and the fluorescent probes to different embryos at different stages to see, at the subcellular level, the glycan-containing cells as the embryos developed. By adding differently coloured probes to embryos at different times, they could also see how cells moved within the embryo and when new cells began producing glycans—observations that could not be made with previous approaches.

The researchers found that zebrafish embryos had a spurt of glycan synthesis about two-and-a-half days after fertilization, and this synthesis was particularly prominent in the jaw, the fins over the gills and the organs that detect scents. Around the jaw area, the researchers saw that the cells producing glycans were proliferating in troughs running from the back, whereas previously labelled cells were restricted to the peaks. Other organs also showed distinct spatial arrangements of cells that produce glycans at different time points.

Though the team has not yet used the imaging system in mouse embryos, a similar system has been demonstrated in mammalian cells. Baskin says techniques involved in their approach, such as confocal microscopy, are standard (Although the fluorescent reagents are not commercially available, Baskin says the lab supplies them to interested parties.)

The limited number of techniques available for studying cells in vivo has long stymied stem cell biologists. Now they have another tool for studying cell behaviour.