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 Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung

nachricht A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Pulverizing electronic waste is green, clean -- and cold

22.03.2017 | Materials Sciences

Astronomers hazard a ride in a 'drifting carousel' to understand pulsating stars

22.03.2017 | Physics and Astronomy

New gel-like coating beefs up the performance of lithium-sulfur batteries

22.03.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>