Genetic switch underlies noisy cell division

Sep 23, 2010 By Richard Merritt
Linchong You's study relied on mouse cells growing in culture - You lab, Pratt School of Engineering

(PhysOrg.com) -- While scientists have spent the past 40 years describing the intricate series of events that occur when one mammalian cell divides into two, they still haven't agreed on how the process begins.

There are two seemingly contradictory theories, which now may be reconciled by a third theory being proposed by Duke University Lingchong You. These findings could provide insights into the initiation of disease, such as cancer, which is marked by uncontrolled cell proliferation.

During proliferation, the within the nucleus of a cell makes a copy of itself, and the cell then splits into two, each half taking with it an exact copy of the of the cell. Theories about the process aren't clear on when it begins because often the same types of cells will begin dividing at different times under identical circumstances.

One of the two prevailing models for explaining cell division says that the beginning of division for any specific cell is just a random event. The second model assumes that there are intrinsic differences between cells that enable some to enter the process earlier than others.

"While both of these models provide a good fit with the experimental data we have, their lack of mechanistic details limit their predictive power and has furthered the debate among cell biologists," You said.

You's team found that a specific known as Rb-E2F has the unique ability to tell some cells to start dividing while at the same time telling other cells to lay low. Rb-E2F is a gene circuit known for its "bistability," which was also demonstrated by the team two years ago. The gene circuit is in all cells and can tell identical cells to live in two states simultaneously, either on or off.

"We have found that a specific gene circuit acts as a 'switch' to tell a cell in an identical population to turn on or off - some respond immediately, some don't," You said. "Looking at key elements in this gene circuit that are determining when a cell enters the division process can reconcile the two schools of thought and could help us better understand this fundamental aspect of cell biology."

Bistability is not unique to biology. In electrical engineering, for example, bistability describes the functioning of a toggle switch, a hinged switch that can assume either one of two positions - on or off.

The results of You's experiments were published on-line in the Public Library of Science (PLoS) Biology.

You's team began by taking an identical population of mouse cells in culture, and then starving them of nutrients, putting all of them in the same state. The cells are essentially in hibernation awaiting a cue to wake up and start dividing, You said. Feeding the cells "wakes" them up.

"The process is much like what happens after a large Thanksgiving meal," You explained. "All the family members sit at the table and celebrate by eating a lot of food. However, after the meal some of the family members will go outside and do something active, like playing football, while others will remain at the table or watch the game on television."

The bistable switch determines which group each cell belongs to.

"We believe that our analysis provides a simple framework reconciling the two schools of thought of cell cycle entry, which has been a source of debate over the past two decades," You said.

You said that knowledge of the precise role of Rb-E2F switch could be helpful to scientists studying cancer by helping to establish a "library" of cancer-causing pathways.

"Using the techniques we developed, scientists can look at an unknown cancer type and by looking at its Rb-E2F profile, and infer what might have gone wrong in the cancer ," You said.

Explore further: How plant cell compartments change with cell growth

Related Stories

Stem-cell activators switch function, repress mature cells

Dec 16, 2009

In a developing animal, stem cells proliferate and differentiate to form the organs needed for life. A new study shows how a crucial step in this process happens and how a reversal of that step contributes to cancer.

Algae Provide New Clues to Cancer

Oct 13, 2006

A microscopic green alga helped scientists at the Salk Institute for Biological Studies identify a novel function for the retinoblastoma protein (RB), which is known for its role as a tumor suppressor in mammalian ...

New evidence that stem cells contain immortal DNA

Jun 27, 2006

EuroStemCell scientists at the Pasteur Institute in Paris have demonstrated one of the body’s most sophisticated ways of regulating the genetic material of stem cells. Their findings, published in Nature Cell Biology, show f ...

Recommended for you

How plant cell compartments change with cell growth

22 hours ago

A research team led by Kiminori Toyooka from the RIKEN Center for Sustainable Resource Science has developed a sophisticated microscopy technique that for the first time captures the detailed movement of ...

Plants can 'switch off' virus DNA

22 hours ago

A team of virologists and plant geneticists at Wageningen UR has demonstrated that when tomato plants contain Ty-1 resistance to the important Tomato yellow leaf curl virus (TYLCV), parts of the virus DNA ...

A better understanding of cell to cell communication

23 hours ago

Researchers of the ISREC Institute at the School of Life Sciences, EPFL, have deciphered the mechanism whereby some microRNAs are retained in the cell while others are secreted and delivered to neighboring ...

A glimpse at the rings that make cell division possible

23 hours ago

Forming like a blown smoke ring does, a "contractile ring" similar to a tiny muscle pinches yeast cells in two. The division of cells makes life possible, but the actual mechanics of this fundamental process ...

User comments : 0