Over the years scientists have learned that planarians mount recovery responses that differ depending on the severity of the injury they suffer. For example, a worm with a cut or a puncture wound reacts at the cellular and molecular levels quite differently from one that loses its head or tail. What has remained unclear, however, is just exactly how these responses are triggered.
Whitehead Institute Member Peter Reddien and two of his former graduate students, Michael Gaviño and Danielle Wenemoser, address this longstanding question this week in the journal eLife, revealing a fascinating interplay of signals between two wound-induced genes.
According to the work of Gavino, Wenemoser, and Reddien, regeneration initiation in planarians is regulated by the expression of the genes Smed-follistatin (or fst) and Smed-activin-1 and -2 (or act-1 and act-2), that together act like a switch. After a planarian is wounded, the type of injury determines the level fst expression——the more extreme the loss of tissue, the higher the level of fst expressed. At puncture wounds, fst expression is low, and regeneration is inhibited. However, following amputation, which results in major loss of tissue, fst levels rise and in turn inhibit Activin proteins, allowing regeneration to begin.
To the researchers' surprise, this interaction only affects regeneration and healing related to injury. Normal maintenance and cell turnover throughout the planarian body continue unaffected when fst is inhibited, even though these activities rely on the same neoblast cell population that creates new tissue during regeneration.
"It's a really great phenotype," says Reddien, who is also a Howard Hughes Medical Institute Early Career Scientist and an associate professor of biology at Massachusetts Institute of Technology. "It's one of the dream phenotypes—to have a defect that's regeneration-specific, where the neoblasts are working. It's just regeneration that isn't working."
Such a phenotype could be a powerful tool in the further exploration of mechanisms that control regeneration. And many questions about these mechanisms remain.
"For example, the animals know how far to grow in regeneration, so they don't make tumorous outgrowths," says Wenemoser, who is now a postdoctoral researcher at Stanford University. "There's some kind of regulation on homeostatic size, so they're not growing out all wild and crazy. There's definitely more to investigate there."
Gaviño agrees, and points out that the fst/act-1/2 switch may ultimately help scientists tease apart regeneration in other organisms, including humans.
"This regulation by activin and follistatin may be conserved in other systems," says Gaviño, who is currently a postdoctoral researcher at Univeristy of California, San Francisco. "There are a lot of hints in the scientific literature that versions of activin or follistatin or both are activated by injury and may play a role in regeneration in other animals, but pinning the role of initiating regeneration to them hasn't happened yet."
This work was supported by the National Institutes of Health grant R01GM080639 and the Keck Foundation.
Written by Nicole Giese Rura
Peter Reddien's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a Howard Hughes Medical Institute Early Career Scientist and an associate professor of biology at Massachusetts Institute of Technology.
"Tissue absence initiates regeneration through Follistatin-mediated inhibition of Activin signaling"
eLife, online on September 10, 2013.
Michael A. Gaviño (1), Danielle Wenemoser (1), Irving E. Wang (1), and Peter Reddien (1).
1. Howard Hughes Medical Institute, Whitehead Institute, and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.
Nicole Rura | EurekAlert!
Progress in Super-Resolution Microscopy
17.12.2018 | Julius-Maximilians-Universität Würzburg
Communication between neural networks
17.12.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
Researchers from the University of Basel have reported a new method that allows the physical state of just a few atoms or molecules within a network to be controlled. It is based on the spontaneous self-organization of molecules into extensive networks with pores about one nanometer in size. In the journal ‘small’, the physicists reported on their investigations, which could be of particular importance for the development of new storage devices.
Around the world, researchers are attempting to shrink data storage devices to achieve as large a storage capacity in as small a space as possible. In almost...
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
17.12.2018 | Studies and Analyses
17.12.2018 | Life Sciences
17.12.2018 | Power and Electrical Engineering