Genetics researchers at Dartmouth Medical School have identified the genes that control cell death during asymmetrical cell division, as reported on April 8 in the Public Library of Science journal. These genes control killer proteins, which dictate whether a cell lives or dies.
Apoptosis, or programmed cell death, plays many developmental and regulatory roles for organisms in both adult and early stages. The gaps between human fingers and toes, for example, form because the cells that would have filled these areas contained activated genes that forced them to die. This process also helps to maintain healthy living cells: in a human adult, between 50 and 70 billion cells are terminated each day, according to the Burnham Medical Institute. Apoptosis also plays a key role during asymmetric cell division. This type of cell division produces two daughter cells, one large and one small. The larger cell lives on but the smaller cell is often terminated for a variety of reasons.
A DMS team led by genetics professor Barbara Conradt and postdoctoral fellow Julia Hatzold has pinpointed the biological mechanism behind this process. The researchers worked on a cell called NSM neuroblast found in the soil nematode Caenorhabditis elegans. This cell divides through asymmetric cell division, producing two daughter cells. The smaller cell always dies off immediately after cell division, a Dartmouth press release says of the researchers’ findings.
Conradt and Hatzold located a gene, egl-1, that is contained in both daughter cells. However, the two proteins, CES-2 and DNJ-11, required to express this gene are inactive in the larger cell. Instead, the cell contains the CES-1 suppressor protein, which renders the gene inactive. The small cell lacks this protein, and is destined to die.
The team also investigated mutant neuroblast cells with an altered CES-1 encoding gene. These cells divided symmetrically, and neither cell was terminated. The geneticists concluded that CES-1 not only controls which cell dies, but is also required for asymmetric cell division.
Strong evidence suggests that this mechanism is similar to ones found in mammals and humans. When a human stem cell divides, it produces another stem cell and a cell that differentiates into a more specialized cell. The specialized cells have the unique ability to either undergo apoptosis or override cell division to stop signals and continue differentiating, a 2005 letter in the journal Nature said. More research into this mechanism may lead to new cancer treatments