Role for microRNAs in limb regeneration

In the March 15th issue of G&D, Dr. Kenneth Poss (Duke University Medical Center) and colleagues reveal that microRNA depletion is a necessary step in tissue regeneration - a discovery with interesting implications for their use in regenerative medicine.

Dr. Poss is excited at the prospect that "there may indeed be microRNAs that when manipulated appropriately could impact and even increase the ability of a damaged human organ to regenerate healthy tissue."

Regeneration, the replacement of damaged or lost body parts, is a shared trait among some animal species – as any youngster who has cut an earthworm in half can attest to. But the repair of damaged tissue and organs in higher animals is also one of the primary goals of current stem cell research.

The common aquarium pet, zebrafish, is an excellent genetic model system, capable of regenerating its spinal cord, retina, heart and fins. First author, Viravuth Yin, and his colleagues focused on fin regeneration, as it entails the coordination of a large number of different cells types to recreate the functional organ.

The scientists noted that many microRNAs were differentially regulated during fin regeneration, but that the expression of one microRNA in particular – miR-133 – showed an antagonistic relationship with fin regeneration: When miR-133 levels are high, fin regeneration is inhibited; When miR-133 levels are low, fin regeneration is promoted.

miR-133 is regulated by the FGF signaling pathway, so by tweaking FGF activity, Dr. Poss and colleagues were able to manipulate miR-133 levels. The researchers found that experimentally increasing miR-133 levels slowed regeneration, while decreasing miR-133 levels enhanced regeneration.

“The finding that microRNA levels are being controlled during appendage regeneration to assist changes in gene expression makes sense, given how important these RNAs are in developmental biology. We were surprised, though, to see that modulating the amount of a single microRNA family could influence regenerative success in zebrafish,” explains Dr. Poss.