Heads or tails? Scientists ID gene key to regenerating flatworms

When cut, a planarian flatworm can regenerate a new head, new tail or even entire new organisms from a tiny fragment of its body--a phenomenon that has puzzled researchers for more than 100 years.
 
Now, scientists in the lab of Peter Reddien, a member of the Whitehead Institute for Biomedical Research and an MIT assistant professor of biology, have discovered a gene required for proper decisions about head-versus-tail polarity in regenerating flatworms.

Their results, published in the Dec. 6 issue of Science online, could help explain how regenerating animals "know" what missing tissues to make.
 
"Evolution has selected for mechanisms that allow organisms to accomplish incredible feats of regeneration," and planaria offer a dramatic example, Reddien said. "By developing this model system to explore the molecular underpinnings of regeneration, we now have a better understanding of … the process."
 
The researchers used a technique called RNA interference to screen a group of genes known to be involved in animal development. 
 
"We discovered that inhibiting the gene Smed-beta-catenin-1 caused animals to regenerate a head instead of a tail at the site of the wound," said Christian Petersen, Whitehead postdoctoral fellow and lead author on the paper. "This resulted in a worm that possessed two oppositely facing heads. Smed-beta-catenin-1 is the first gene found to be required for this regeneration polarity."
 
Genes very similar to Smed-beta-catenin-1 are found in animals ranging from jellyfish to humans, and they have been implicated in posterior tissue specification in frogs, sea urchins and many other animals. 
 
The researchers then went on to study the expression of a family of genes associated with regeneration. They found that different members of the Wnt gene family were active at different locations across the planarian's head-to-tail axis. These results suggest that Smed-beta-catenin-1 may be active in the tail region and inhibited in the head region by the regulated expression of these Wnt genes.
 
Additionally, the researchers found that Smed-beta-catenin-1 plays a role in ongoing cell replacement in planaria that have not been challenged to regenerate. When the gene was inhibited, these animal's tails began changing into heads.
 
The researchers hope that future work on regeneration polarity and Smed-beta-catenin-1 will yield a better understanding of the molecular mechanisms of regeneration.