We try to ask cells to do what they already know how to do. In approaching problems, we have attempted to use an existing biological mechanism to attain our goals, especially when developing new tools. For example, during the last 2 years, another very talented postdoc in the lab, Michael Buszczak, has been fusing genes to green fluorescent protein (GFP), in vivo, on a large scale by taking advantage of the biology of Drosophila transposable elements [bits of DNA that can move from place to place in an organism’s genome]. About 2,000 fruit fly strains have been produced so far in which a different gene is fused to GFP. Since each of these GFP-fusion proteins is produced using the endogenous gene’s normal control circuits, they are likely to reveal the gene’s normal pattern of expression. There is also an excellent chance of seeing the normal tissue distribution and subcellular location of the gene product. A large collection of such strains will allow us to map the cellular structure of Drosophila tissues at the single-cell level and to identify genes involved in many biological processes—including stem cells. Eventually, it may be possible to insert even more sophisticated reporters—for example, those that fluoresce when certain signals are sent or when a cell activates other internal processes.

We understand relatively little of what goes on in multicellular organisms at the level of molecular processes within specific, individual cells. Not too many years ago, the general feeling was that insects didn’t have stem cells. Turns out that it’s not that way at all. And now, in some quarters, you’d think that biology is practically all figured out: We just need computer models and we’ll understand the whole thing. In reality, we suspect that one could take virtually any tissue, even tissues that have been studied for a long time, and find new cell types and new interactions that are important and unexpected. For example, we found a new epithelial stem cell within the germline stem cell niche. It produces a small set of somatic cells that interact with early germ cells. We suspect that the interactions between these cells and early differentiating germ cells are among the most critical in determining whether reversion happens or development continues. We didn’t even know these cells existed, and now we see that they are maintained by their own set of stem cells, and that both sets of stem cells and their progeny signal back and forth. It’s a small example of a type of analysis that remains to be done with many metazoan tissues.

Photo: ©Paul Fetters

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