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

06.08.2014

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.

“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
212-327-8982
newswire@rockefeller.edu

Zach Veilleux | newswise
Further information:
http://www.rockefeller.edu

Further reports about: Cell’s Embryonic French Rockefeller concentration fate pipes

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>