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Zebrafish Regenerative Ability to Help in Humans


March 2008

Duke University Medical Center biologists have discovered a molecular circuit breaker that controls a zebrafish's remarkable ability to regrow missing fins.

Zebrafish can regenerate organs and tissues, including hearts, eye parts and fins. When a fin is lost, the fish regenerates a perfect copy in two weeks by orchestrating the growth of many tissue types, including bone, nerves, blood vessels, connective tissue and skin.

Hope is that understanding how zebrafish repair themselves will lead to new treatments for human conditions caused by damaged tissue, such as heart failure, diabetes and spinal cord injuries.

The regeneration regulator is one of a group of recently discovered molecules called microRNAs: small pieces of ribonucleic acid (RNA) that each can potentially control the activity of dozens of different genes. In humans, microRNAs play important roles in cell growth and death, among other functions. There are hundreds of kinds of microRNAs, and scientists are constantly discovering new roles they play.

In zebrafish, one or more microRNAs appear to be important to keep regeneration on hold until the fish needs new tissue, the Duke researchers say. In response to an injury, the fish then damp down levels of these microRNAs to aid regrowth. The team discovered that the ability of zebrafish to replace amputated fins is particularly sensitive to levels of a particular microRNA called miR-133.

The discovery makes sense because any animal that can rapidly grow new tissue needs to keep the system in check, said senior author Kenneth Poss, Ph.D., assistant professor of cell biology. "They probably need to have mechanisms to reduce the potential for unwelcome growth. The implication is that in order to make human tissue regenerate more effectively, we might want to look at some of these microRNAs as potential targets."

The results appear in the March 15, 2008 issue of the journal Genes & Development. Postdoctoral scholar Viravuth Yin, Ph.D., a member of Poss' lab, is first author on the study. Funding was provided by the National Institutes of Health, the American Heart Association, the Whitehead Foundation and Pew Charitable Trusts.

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