Found: Killer Gene Switches That Regulate Cell Fate

April 10, 2008

Dartmouth Medical School geneticists have pinpointed a mechanism by which cells are destined to live or die, assuring the development of a healthy organism. Their discovery may offer clues to controlling the fate of cancer cells.

The work is reported April 8 in PLoS (Public Library of Science) Biology by Dr. Barbara Conradt, associate professor of genetics, and Dr. Julia Hatzold, postdoctoral fellow.

Dr. Barbara Conradt

Dr. Barbara Conradt

The discovery links two biological processes essential for the vitality and diversity of an organism: asymmetric cell division, which creates daughter cells that are different, and apoptosis, which prompts unwanted or defective cells to die.

"Asymmetric cell division makes sure you generate daughters that have different fates and apoptosis is programmed death that eliminates superfluous cells," said Conradt. "Both processes are so important for a functional organism and we show for the first time that they directly connect. Factors that cause asymmetry directly regulate a killer gene."

The researchers looked at the round worm gene called egl-1, which is implicated in apoptosis and related to a well known gene group involved in several human cancers and perhaps other diseases. Building on her prior studies of egl-1, Conradt with Hatzold identified the molecular machinery that regulates how a worm cell called NSM neuroblast divides into two asymmetrical daughter cells, and then terminates the smaller cell.

Although present in both sisters, the egl-l killer gene is turned on only in the smaller sibling that dies. One protein called CES-1 blocks the expression of egl-1 and two other proteins activate it. Both daughter cells have the activator complex to turn on the killer gene, but only the larger survivor has the suppressor protein that keeps off egl-l, the researchers observed.