Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

An embryonic cell’s fate is sealed by the speed of a signal

05.08.2014

When embryonic cells get the signal to specialize the call can come quickly. Or it can arrive slowly. Now, new research from Rockefeller University suggests the speed at which a cell in an embryo receives that signal has an unexpected influence on that cell’s fate. Until now, only concentration of the chemical signals was thought to matter in determining if the cell would become, for example, muscle, skin, brain or bone.

“It turns out that if ramped up slowly enough an otherwise potent signal elicits no response from the receiving cells. Meanwhile, a pulsing, on-off signal appears to have a stronger effect than a constant one,” says researcher Ali Brivanlou, Robert and Harriet Heilbrunn Professor and head of the Laboratory of Molecular Vertebrate Embryology. This research is the latest collaboration between Brivanlou and Eric Siggia, Viola Ward Brinning and Elbert Calhoun Brinning Professor at Rockefeller’s Center for Studies in Physics and Biology.


Tempting fate. To visualize cells’ responses to the signals that ultimately lead them to choose a fate, the researchers engineered a protein involved in this response, Smad4, to glow. In response to a pulse of signal molecules, Smad4 moves into the dark nuclei of the cells, causing them to glow briefly.

“Until now, it has not been feasible to test how speed or other temporal dynamics affect a cell’s response to a signal. However, by adapting technology that allows for very precise control over these aspects, we found unequivocal evidence that signal level alone does not determine a cell’s fate. Its presentation is also extremely important,” Siggia says.

Together, the team dubbed their discovery “speed fating.” Their work will be published in August in Developmental Cell.

Biologists know a cell determines its location in an embryo and, as a result, its future role, based on chemical cues from its neighbors. About 50 years ago, the developmental biologist Lewis Wolpert proposed that this determination hinges on the concentration of the signal to which a cell is exposed: Go above a certain threshold and you get one fate, below and you get a second. His proposal is known as the French flag model, after a tri-color graph used to represent three cell fates based on those cells’ positions with respect to the source of the signal.

Prior work from Brivanlou and Siggia had cast doubt on the sole importance of concentration. Using a common developmental signaling pathway known as TGF-β, the team documented what is known as an adaptive response from cells exposed to TGF-β signaling molecules. This response peaked then declined over time, even though the signaling molecules remained present. (Think of how a constant noise eventually blends into the background.) If concentration was the sole factor responsible for a response, then the response should have continued as long as the signal was present.

To follow up on this work, Benoit Sorre, a former Rockefeller postdoc now at the University of Paris Diderot, adapted a system that makes use of miniaturized networks of pipes, pumps, valves and sample chambers all under computer control. For experiments, he teamed up with Aryeh Warmflash, the postdoc who lead the previous TGF-β work. Together, they worked with mouse cells that have the potential to differentiate into muscle, or cartilage and bone. Progenitor cells like these, which can differentiate into a limited set of tissues, are the offspring of stem cells. In experiments using Sorre’s new system, the researchers exposed these progenitor cells to signaling molecules from the TGF-β pathway, and then recorded the cells’ responses to see if the signal activated the pathway that leads them to choose a fate.

Sorre and Warmflash started with a continuous signal. As Warmflash’s previous work suggested, this finger-stuck-on-the-buzzer approach did not produce a continuous response from the cells. Instead, the response declined. A second set of tests showed a series of brief pulses of signal produced a greater response than one continuous signal.

Gradually increasing the concentration of the signal, however, appeared to have the opposite effect. The researchers ramped up the concentration of the signal over periods as brief as five hours or as long as 40 hours. The longer the period and the slower the rate of increase, the weaker the cells’ response. The cells subjected to a 40-hour run barely registered at all.

Based on these experiments, the team formulated a mathematical model to describe how a cell in an embryo may infer its position in relation to the source of the signal. In this way, the research offers a new take on the French flag model: It is still true that the fates of three cells can be mapped out based on their position, but the cells appear to arrive at these fates more rapidly than previously thought, thanks to the adaptive response that takes into account both the level and speed of a signal.

“This finding is another instance of a productive collaboration between biologists and physicists. Neither group, biologists or physicists, could have realized this result working alone,” Siggia says.

Zach Veilleux | Eurek Alert!
Further information:
http://newswire.rockefeller.edu/2014/08/04/an-embryonic-cells-fate-is-sealed-by-the-speed-of-a-signal/

Further reports about: Biology Laboratory Molecular evidence experiments offspring pathway

More articles from Life Sciences:

nachricht No chance for house dust mites
06.05.2015 | Hohenstein Institute

nachricht Expedition Genomics Lab: the mobile revolution in genetic analysis
06.05.2015 | MUSE Museo delle Scienze

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spray drying the precision particle under the virtual magnifying glass

Spray drying is a common manufacturing process, used in the production of ceramic granulate for technical components or dental prostheses as well as dissolvable medicinal substances, food additives and in the processing of milk into powder. Using computer simulation methodology developed by scientists at the Fraunhofer Institute for Mechanics of Materials IWM, a more comprehensible understanding can now be gained of the behavior of particles in solvent during the spray drying process. This allows powder and granulate manufacturers to specifically adjust the properties of their products while reducing waste.

Previously, it was unusual for granule and powder producers to use granulation simulations to improve their products. For new product development or process...

Im Focus: The random raman laser: A new light source for the microcosmos

Texas A&M University researchers demonstrate how a narrow-band strobe light source for speckle-free imaging has the potential to reveal microscopic forms of life

In modern microscope imaging techniques, lasers are used as light sources because they can deliver fast pulsed and extremely high-intensity radiation to a...

Im Focus: Pulsar with widest orbit ever detected

Discovered by high school research team

A team of highly determined high school students discovered a never-before-seen pulsar by painstakingly analyzing data from the National Science Foundation's...

Im Focus: Erosion, landslides and monsoon across the Himalaya

Scientists from Nepal, Switzerland and Germany was now able to show how erosion processes caused by the monsoon are mirrored in the sediment load of a river crossing the Himalaya.

In these days, it was again tragically demonstrated that the Himalayas are one of the most active geodynamic regions of the world. Landslides belong to the...

Im Focus: Through the galaxy by taxi - The Dream Chaser Space Utility Vehicle

A world-class prime systems integrator and electronic systems provider known for its rapid, innovative, and agile technology solutions, Sierra Nevada Corporation (SNC) is currently developing a new space transportation system called the Dream Chaser.

The ultimate aim is to construct a multi-mission-capable space utility vehicle, while accelerating the overall development process for this critical capability...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Green Summit 2015: the summit of the essential

05.05.2015 | Event News

HHL Energy Conference on May 11/12, 2015: Students Discuss about Decentralized Energy

23.04.2015 | Event News

“Developing our cities, preserving our planet”: Nobel Laureates gather for the first time in Asia

23.04.2015 | Event News

 
Latest News

Expedition Genomics Lab: the mobile revolution in genetic analysis

06.05.2015 | Life Sciences

How noise changes the way the brain gets information

06.05.2015 | Life Sciences

A model approach for sustainable phosphorus recovery from wastewater

06.05.2015 | Ecology, The Environment and Conservation

VideoLinks
B2B-VideoLinks
More VideoLinks >>>