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 A new potential biomarker for cancer imaging
05.02.2016 | Universiti Putra Malaysia (UPM)

nachricht NIH researchers identify striking genomic signature shared by 5 types of cancer
05.02.2016 | NIH/National Human Genome Research Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Automated driving: Steering without limits

OmniSteer project to increase automobiles’ urban maneuverability begins with a € 3.4 million budget

Automobiles increase the mobility of their users. However, their maneuverability is pushed to the limit by cramped inner city conditions. Those who need to...

Im Focus: Microscopy: Nine at one blow

Advance in biomedical imaging: The University of Würzburg's Biocenter has enhanced fluorescence microscopy to label and visualise up to nine different cell structures simultaneously.

Fluorescence microscopy allows researchers to visualise biomolecules in cells. They label the molecules using fluorescent probes, excite them with light and...

Im Focus: NASA's ICESat-2 equipped with unique 3-D manufactured part

NASA's follow-on to the successful ICESat mission will employ a never-before-flown technique for determining the topography of ice sheets and the thickness of sea ice, but that won't be the only first for this mission.

Slated for launch in 2018, NASA's Ice, Cloud and land Elevation Satellite-2 (ICESat-2) also will carry a 3-D printed part made of polyetherketoneketone (PEKK),...

Im Focus: Sinking islands: Does the rise of sea level endanger the Takuu Atoll in the Pacific?

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister picture is being painted evoking the demise of the island states and their cultures. Are the effects of sea-level rise already noticeable on reef islands? Scientists from the ZMT have now answered this question for the Takuu Atoll, a group of Pacific islands, located northeast of Papua New Guinea.

In the last decades, sea level has been rising continuously – about 3.3 mm per year. For reef islands such as the Maldives or the Marshall Islands a sinister...

Im Focus: Energy-saving minicomputers for the ‘Internet of Things’

The ‘Internet of Things’ is growing rapidly. Mobile phones, washing machines and the milk bottle in the fridge: the idea is that minicomputers connected to these will be able to process information, receive and send data. This requires electrical power. Transistors that are capable of switching information with a single electron use far less power than field effect transistors that are commonly used in computers. However, these innovative electronic switches do not yet work at room temperature. Scientists working on the new EU research project ‘Ions4Set’ intend to change this. The program will be launched on February 1. It is coordinated by the Helmholtz-Zentrum Dresden-Rossendorf (HZDR).

“Billions of tiny computers will in future communicate with each other via the Internet or locally. Yet power consumption currently remains a great obstacle”,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

DATE 2016 Highlighting Automotive and Secure Systems

26.01.2016 | Event News

 
Latest News

A new potential biomarker for cancer imaging

05.02.2016 | Life Sciences

Graphene is strong, but is it tough?

05.02.2016 | Materials Sciences

Tiniest Particles Shrink Before Exploding When Hit With SLAC's X-ray Laser

05.02.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>