Gene determines when cells live or die.

When an amphibian makes the leap from tadpole to toad, the cells in its tail kill themselves because they're no longer needed. Biologists call this phenomenon programmed cell death, or apoptosis. It's a normal part of animal development, but no one knows how it works

Now, researchers studying roundworms have uncovered a clue to the mystery. A cell's fate, they find, teeters on a single gene that keeps the built-in suicide program from starting up.

"The observation that lots of cells in the animal need something in them to continuously protect them from drying is very intriguing. It's the first time it's ever been shown that such a thing could exist," says molecular biologist Ronald E. Ellis of the University of Wisconsin-Madison.

Working at the Howard Hughes Medical Institute at the Massachusetts Institute of Technology in Cambridge, Ellis and his colleagues studied the roundworm Caenorhabditis elegans and found that a gene called ced-9 acts as a switch to regulate programmed cell death. In C. elegans mutants with the ced-9 acts as a switch to turned on, cells that normally would have died during the animal's development survived instead. Conversely, in roundworms with a mutation that turned off the gene, cells that normally would have lived committed suicide, the researchers report in the April 9 NATURE.

With ced-9 turned off, "cells that were supposed to survive and became neurons or muscles or some other kind of cell were killing themselves," says Ellis. "The animals eventually died."

Although the exact mechanism underlying this process remains unclear, ced-9 appears to control two other genes, ced-3 and ced-4, previously found to direct a roundworm cell's suicide process. Ellis and his co-workers discovered that ced-9 had no effect in mutuant roundworms lacking these two genes. "The switch doesn't matter if there's no machine at the other end," Ellis explains.

While C. elegans consists of a mere 1,090 cells, biologists believe that studies of programmed cell dealth in this simple model will help them understand how the process works in more complicated animals, including humans. In fact, ced-9 seems to parallel a gene called bcl-2, which controls the suicidal tendencies of B- and T-cells in the human immune system, says Stanley J. Korsmeyer of the Washington University School of Medicine in St. Louis, who studies apoptosis in humans.

"Bcl-2 has implications for how ced-9 may act," Korsmeyer says, "while ced-9 has implications for the regulation of cell death in mammals."