Fish fins and microRNAs

Source: Cold Spring Harbor Laboratory, Duke University Medical Centre

US researchers have discovered a molecular circuit breaker that controls a zebrafish's remarkable ability to regrow missing fins, according to a new study from Duke University Medical Center.

In the March 15 issue of Genes & Development, Dr. Kenneth Poss of the 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.

Regeneration, the replacement of damaged or lost body parts, is a shared trait among some animal species, but the repair of damaged tissue and organs in higher animals is also one of the primary goals of current stem cell research.

Zebrafish are capable of regenerating their spinal cord, retina, heart and fins. First author Viravuth Yin and his colleagues focused on fin regeneration, as it entails the co-ordination of a large number of different cells types to recreate the functional organ.

The researchers 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 signalling pathway, so by tweaking FGF activity, 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," Poss said.

"We were surprised, though, to see that modulating the amount of a single microRNA family could influence regenerative success in zebrafish."

"Our work shows microRNAs appear to have an important role in regenerating complex tissues. Further studies could help us discover potential ways to stimulate this ability in mammals."