The discovery creates an unexpected new path to follow in the effort to understand the biochemical steps behind cells' movement, a critical aspect of embryonic development and the spread of cancer. The work is described in the July 8 issue of Cell.
By studying fruit flies engineered to make extra use of random genes, the Hopkins team discovered that a protein called "inhibitor of apoptosis-1" (or IAP) can restore the tightly choreographed cellular movement that naturally occurs in fruit fly ovaries as egg cells mature.
"This discovery was completely unexpected," says Denise Montell, Ph.D., professor of biological chemistry in Johns Hopkins' Institute for Basic Biomedical Sciences. "Based on what was known about this protein's function in blocking cell death, there would have been no way to predict its involvement in cell migration."
Instead, graduate student and now postdoctoral fellow Erika Geisbrecht and Montell relied on "forward genetics," an approach in which the scientists alter the expression of random genes, look for a specific effect in the resulting flies and then figure out which gene was affected.
In Geisbrecht's experiments, a small number of cells in the fruit fly ovaries had a dysfunctional protein called Rac, which caused those cells not to move properly and the flies to be sterile. Geisbrecht then randomly increased production of other genes in the cells and looked for flies whose fertility was restored, an obvious sign that their cellular choreography had returned to normal.
"The idea is simple -- if the cell migration problem improved, the overexpressed gene must have fixed or compensated for the lack of functional Rac," says Montell.