A worm named Schmidtea mediterranea has the unique ability to regenerate not just its body, but also its head and brain. Now, scientists studying the worm have discovered one of the genes that allows it to accomplish this amazing feat.

The gene, called "smed-prep," regulates the location and structure of the flatworm's brain during regeneration. When the gene is absent, the worm forms a stump with random junk from other parts of its body, but no brain. When it's expressed in other areas of the body, heads can be made to sprout from anywhere.

"One of the main goals in the lab was to understand the mechanisms that allowed this worm to regenerate its head, brain and sensory organs," said molecular biologist Aziz Aboobaker of the University of Nottingham, lead author of the paper published in PLoS Genetics April 22. "It's a big problem because you have to make this all from the old tissue. The cells have to mobilize, migrate to the right place and differentiate."

The S. med worm is small, but has complex organs and a primitive bilateral brain. Not only can it regenerate its head and brain, but each piece you cut off (down to about 1 millimeter) can re-grow into a complete organism. The worm can do this because about 25 percent of its cells are stem cells, which can differentiate into any cell type.

To find the gene, Aboobaker scanned the worm's genome looking for developmental genes. After testing several other genes, Aboobaker's team stumbled upon smed-prep, whose expression was concentrated in the worm's head region.

To see how the gene affected the worm's ability to regenerate, they tricked the cell into destroying any messenger RNA or protein made from it, using interfering RNA. The worms who had their gene expression cut down were unable to regenerate their brains after amputation, but other aspects of the regeneration process were unaffected.

"That's the interesting thing, we haven't killed them off, they are still healthy," Aboobaker said. "They just can't navigate or find food."

Humans have a gene that is similar in biochemical structure and genetic code to smed-prep, but its function in humans is unknown. Related genes in other vertebrates, like mice and zebrafish, are expressed in the brain during embryo formation.

"The most interesting aspect of this paper is its evolutionary perspective," said cell biologist Alejandro Sánchez Alvarado, of the University of Utah, because C. elegans (a commonly studied worm) and drosophila (the fruitfly) do not appear to have evolved a directly corresponding gene. Alvarado previously discovered two other genes involved with S. med's head regeneration process.

The worm and its properties can teach us more about human health, because it's a good model system to learn about stem cells, regeneration and aging, said Aboobaker.

"You can't just make neurons from stem cells, then insert them into your brain, because you have no idea what would happen," he said. "If you ask someone to make you a brain from a ball of tissue, they won't be able to, because we don't know how. But the worm does."

The team's next step is to determine what other genes are regulated when smed-prep is turned on and off. "Finding [smed-prep] means you can find which genes don't turn on properly when it is knocked down," Aboobaker said. "Those are the genes that must be involved in this network that makes the brain."

Image: Wikimedia Commons/Alejandro64

See Also:

Citation: "The TALE Class Homeobox Protein Smed-prep Defines the Anterior Compartment for Head Regeneration." By Daniel A. Felix and A. Aziz Aboobaker. PLoS Genetics Vol. 6, Issue 4, April 22, 2010.