Planaria deploy an ancient gene expression program in the course of organ regeneration

It’s hard to feel kinship with planaria worms, the tiny aquatic flatworms most often found in standing water and resembling brown tubes with rudimentary “eye-spots” and a feeding apparatus – the pharynx – that doubles as an excretory tract. And yet, the Sánchez Alvarado Lab has used them as a promising model system for accelerating mammalian regeneration.

“When mammals are severely injured, they just heal the wound and call it a day,” explains Alejandro Sánchez Alvarado, PhD. A planarian, however, has the ability to heal injured areas and regenerate its body. This capacity is not what’s surprising, as biologists know that thirty percent of planarian body cells are stem cells; the ability of these cells to identify what has been lost and regenerate the correct cells, however, has mystified researchers.

Stowers researchers shed light on this mystery by identifying the genes worms use to rebuild an amputated pharynx. They report that near the top of the pharynx regeneration hierarchy is a master regulator called FoxA and go on to reveal how planarian stem cells sense the loss of a particular structure on a molecular level.

“Currently, we think that FoxA triggers a cascade of gene expression that drives planarian stem cells to produce all of the different cells of the pharynx, including muscle, neurons, and epithelial cells,” says Carrie Adler, PhD, a postdoctoral fellow who led the study. “The next question is how FoxA gets stimulated in the first place in only some stem cells.”

Beyond the newly identified role of FoxA, Sánchez Alvarado concludes that his lab’s work cements planaria’s place as a key model system to analyze regeneration or stem cell activity. “Planaria’s simplicity is what makes it such a fruitful system,” he says. “If we used salamanders for these studies it would take ninety days to do an experiment. I want answers to these questions yesterday, not years from now.

The study was published in the April 15, 2014 issue of the online journal eLife.