New advances in molecular tagging may one day offer deeper insights into the development of diseases such as cancer and heart disease. Now in its infancy, the technique has been applied to tracking the development of the zebrafish embryo in vivo using noninvasive imaging of sugar molecules.

Sugars at the cell surface contain much information about a cell's physiological state. For example, changes in their structures may act as markers of changes in gene expression that occur during cell development and disease progression. Therefore, these sugars are prime targets for diagnostic in vivo imaging, but have so far been poor candidates because they are incompatible with genetically encoded reporter molecules.

The new technique is the latest advance in 'click chemistry', or the linking of molecules that are otherwise not readily joined together. A popular version of these reactions uses a copper catalyst to link azides, small chemical groups that are stable in vivo, with activated alkynes. The azide groups are attached to sugars, which are then incorporated into the cells of interest. In the presence of copper, the azides react with fluorescently labeled alkynes, allowing researchers to track the sugars. But copper is toxic to living organisms, limiting the use of this technique to ex vivo applications.

To enable in vivo imaging of the sugars, Carolyn R. Bertozzi and colleagues at the University of California Berkeley modified the reaction by eliminating the need for the copper catalyst. They achieved this by bending the alkynes into rings, allowing them to react quickly with the azides without requiring a catalyst. Bertozzi and colleagues previously reported on the use of this technique to stain rodent tissue samples.

Now, they have taken the next step and used the technique to track cell-surface sugars during embryonic development in vivo in zebrafish (Science 320, 664–667; 2008). The zebrafish was a good candidate for this study because its development is well-documented, it is frequently used in biomedical research, and it is amenable to optical imaging. Bertozzi's group was able to simultaneously track the distribution of different sugar groups throughout embryonic development and detect patterns that could not have been observed using conventional molecular imaging methods. They recorded bursts of sugar synthesis in the jaw, pectoral fins and olfactory organs 60 hours after fertilization.

So far the technique has been used in rodents and in fish, and the researchers believe it will function in other organisms as well. Future studies will aim to apply the technique to tracking cells in tumors and diseased blood vessels.