( s a protective mechanism in the hindlim...)MicroRNA may have fail-safe role in limb development

"A large body of evidence indicates this new class of regulators is not something to turn things off in the first place, but a fail-safe," said Clifford Tabin, Ph.D., a professor of genetics at Harvard Medical School and senior author of the research. "You don't want cells in a hindlimb seeing cells that should only be in a forelimb - it would create a defective limb. So you not only want to shut the faucet tight on the wrong cells, you want to shove a towel into it, too, to really make sure the wrong thing doesn't leak out. One way of doing that is with microRNA."

Researchers looked at gene activity in chicken embryos and in mice, finding miR-196 silences a chemical important for transferring information from DNA to RNA within a cell - a transcription factor.

"It's turning off a transcription factor in the hindlimb that is important for forelimb development," Harfe said. "But it still doesn't explain why a hindlimb is a hindlimb and a forelimb is a forelimb."

The next step in the research is to observe limb development in mice engineered to not express miR 196.

"The authors have shown a role for miR 196 in limb development," said John Fallon, the University of Wisconsin's Harland Winfield Mossman professor of anatomy. "People talked about ways microRNA may have a role in embryonic development, and this work is a solid contribution that supports that idea. Researchers have also been looking for differences between gene expression in forelimbs and hindlimbs, with little success. This paper suggests there is a new mechanism to control the fidelity of protein expression in the limbs through microRNA expression. That is a hypothesis that people in the field will have to test, but it is strongly supported by their research."