Scientists have for the first time completed a survey of gene function in a highly regenerative species of worm that could offer important insights into cell regrowth in humans.

Putting the abilities of Wolverine in the movie X-Men to shame, a small piece of a planarian worm can regenerate an entire new body. The worm’s ability to regenerate is so powerful that a tissue fragment only 1/279 of the worm’s length can grow into a new animal.

Alejandro Sánchez Alvarado, professor of neurobiology and anatomy at the University of Utah School of Medicine, used a tool called RNA interference to identify 240 genes responsible for regeneration in planarians, also known as flatworms. The work of Dr. Sánchez Alvarado and his team is published in the May issue of Developmental Cell.

“This study introduces the possibility of carrying out systematic gene function studies in an organism that traditionally has not been accessible to genetics,” said Sánchez Alvarado. “The importance of this advance lies in the biological attributes displayed by planarians — that is, abundant adult stem cells responsible for the extensive and robust regeneration of amputated parts, as well as the continuous renewal of differentiated tissues (tissue homeostasis).”

It’s too soon to tell whether research into planarian worms might one day let doctors regrow amputated limbs or diseased organs in people. Nevertheless, since many of the genes found in flatworms are also present in humans, scientists believe they may provide insights into how to use adult stem cells to replace diseased or damaged human tissue.

Unlike the most common organisms studied by scientists, such as the nematode Caenorhabditis elegans and the fruit fly Drosophila, flatworms have the ability to use adult stem cells and so regenerate when necessary.

“Planarians share with humans both adult stem cells and tissue homeostasis,” said Sánchez Alvarado. “These attributes, however, are not saliently manifested in current invertebrate model systems such as Drosophila and C. elegans.”

Sánchez Alvarado’s work offers the latest genetics research success that used RNA interference, or RNAi, which won Science magazine’s Breakthrough of the Year in 2002.

“RNAi allows us to directly understand the function of individual genes in a given organism,” said Tim Littlewood, a parasitologist at the Natural History Museum in London. “It is a relatively fast and reliable means of attributing function to genes.”

To find the genes that are involved in regeneration in planarians, Sánchez Alvarado and colleagues used RNAi to “knock out” more than a thousand genes, and then looked at how the flatworms with the silenced genes grew.

As a result of these studies, candidate regulators of stem cells and regeneration were identified along with genes that appeared to be critical for normal physiological processes.

“Planarians are exciting in a regeneration context because in contrast to so many other animals, they have a very well-established system to switch cell differentiation and cell division on and off on demand — apparently without the risk of having to deal with uncontrolled, cancerous growth or malformation,” said Nico Michiels, a flatworm researcher at the University of Tuebingen in Germany.

As well as understanding regeneration, silencing planarian genes may also help in studying human disease. Thirty-eight of the genes Sánchez Alvarado and his team silenced are related to human genes associated with various diseases, including cancer. And another 35 may shed light on parasitic flatworms. These include Schistosoma mansoni, which annually causes disease in millions of people.

“It’s exciting research,” said Littlewood. “A flatworm model will enable us to delve deeper into the functional genomics of some major human flatworm pathogens, including tapeworms and liver flukes.”

Just don’t expect real-life Wolverines just yet.

“It would not be appropriate to speculate on regeneration of human tissue with our current understanding,” said Sánchez Alvarado.

by Rowan Hooper

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