Tissue loss triggers regeneration in planarian flatworms

Sep 03, 2013 by Nicole Giese Rura

Unlike humans, planarian flatworms have the remarkable ability to regrow any missing body part, making them an ideal model with which to study the molecular basis of regeneration.

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, 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 , 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 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."

Explore further: Deep sea fish eyesight similar to human vision

More information: "Tissue absence initiates regeneration through Follistatin-mediated inhibition of Activin signaling" eLife, online on September 10, 2013.

Related Stories

Solving the mysteries of regeneration

Aug 20, 2013

Few animals can rival the amazing regeneration abilities of the flatworms known as planarians: When the worms' tails or heads are cut off, they grow new ones, and even a tiny piece of planarian tissue can ...

Ancient gene gives planarians a heads-up in regeneration

May 12, 2011

A seldom-studied gene known as notum plays a key role in the planarian's regeneration decision-making process, according to Whitehead Institute scientists. Protein from this gene determines whether a head or tail will regrow ...

Planarians offer a better view of eye development

Aug 02, 2012

Planarian flatworms have come under intense study for their renowned ability to regenerate any missing body part, even as adults. But now they may take on a starring role as a model system for studying eye development and ...

Recommended for you

Dogs hear our words and how we say them

Nov 26, 2014

When people hear another person talking to them, they respond not only to what is being said—those consonants and vowels strung together into words and sentences—but also to other features of that speech—the ...

Amazonian shrimps: An underwater world still unknown

Nov 26, 2014

A study reveals how little we know about the Amazonian diversity. Aiming to resolve a scientific debate about the validity of two species of freshwater shrimp described in the first half of the last century, ...

Factors that drive sexual traits

Nov 26, 2014

Many male animals have multiple displays and behaviours to attract females; and often the larger or greater the better.

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.