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. A group of researchers writing in Genes & Development focused on fin regeneration, as it entails the coordination of a large number of different cells types to recreate the functional organ.
Their study reveals that microRNA depletion is a necessary step in tissue regeneration – a discovery with interesting implications for their use in regenerative medicine.
Dr. Kenneth Poss of Duke University Medical Center said he 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.”
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
Article: Viravuth P. Yin, J. Michael Thomson, Ryan Thummel, David R. Hyde, Scott M. Hammond, and Kenneth D. Poss, Fgf-dependent depletion of microRNA-133 promotes appendage regeneration in zebrafish, Genes & Development, March 15 2008