Same gene in fly, human heals skin

UCSD scientists study the process

By Bruce Lieberman

UNION-TRIBUNE STAFF WRITER

April 15, 2005

NELVIN CEPEDA / Union-Tribune

UCSD researchers William McGinnis (left) and Joe Pearson studied genes used by flies to repair skin wounds. Others have found that such a gene is also at work in humans.

Life is short and filled with peril for the fly, so the insect needs a way to heal the cuts and bruises that come with buzzing into windows and getting swatted by humans, among other hazards.

How the fly's genes trigger healing is the subject of a University of California San Diego study appearing today in the journal Science .

The biologists are not so concerned with helping flies as they are with understanding the genetic signals that direct human cells to close a wound. The knowledge might lead to novel approaches for accelerating healing, preventing scars and even fighting skin cancer.

The UCSD scientists identified a gene that triggers wound repair in a type of fruit fly called Drosophila melanogaster .

Remarkably, this gene is responsible for prompting the same response in mammals, including humans, according to a separate study by Australian researchers that is also featured in today's Science .

The gene has been part of the DNA of both flies and mammals since they last shared a common ancestor about 700 million years ago.

"When you look at the skin of a fruit fly and the skin of a mouse or human, they don't look similar," said William McGinnis, whose UCSD lab conducted the fruit fly analysis. "Yet, when you look deeper at a level of the genes that control the formation of a skin barrier, there you see similarities. That was very much a surprise."

The Drosophila fruit fly is a workhorse of genetics that scientists have examined for a century. The fly – along with the tiny worm Caenorhabditis elegans , the zebra fish and the mouse – is among a handful of organisms that researchers use to study human development and disease.

Fruit flies are prime study subjects because they're cheap, they reproduce rapidly and they have a short life span – about two weeks. Scientists also can easily engineer their DNA to make mutants that lack one or more genes.

"You can do any manipulation on a fly, and there will be no groups that object to mass killing of fruit flies," McGinnis said.

The idea for the UCSD report came from Kimberly A. Mace, a postdoctoral researcher in McGinnis' lab. Mace, who now examines the genetics of wound healing at UC San Francisco, was studying the embryos of mutant flies at UCSD.

She observed that the surface of the developing flies displayed lesions caused by abnormal development. In other words, the cells of the growing embryos were not connecting to one another properly, creating open "wounds" that then scarred over.

By scrutinizing the fly's DNA with powerful computers, Mace and her colleagues were able to identify a single gene, called "grainyhead," that triggers several steps involved in closing the wounds.

The odd name actually makes sense among geneticists, who routinely label a newly discovered gene after some characteristic of a mutant that does not possess the gene.

Drosophila fruit fly embryos that are engineered without the grainyhead gene develop tiny granules, or grain-shaped tissue, on their heads.

Pinpointing the genes involved in healing surface wounds, and how they interact with one another, could reap huge medical benefits, scientists said.

One advance might involve manipulating human genes to accelerate wound healing. That could mean more rapid recovery from surgery, less scarring, even quicker recovery time for soldiers suffering from battlefield wounds, McGinnis said.

In addition, Mace said, scientists might better understand cancer. Healing requires genetic signals that trigger cells surrounding a wound to proliferate, migrate toward the lesion and then, once the cut is filled in, stop multiplying.

That genetic signal to stop is somehow lost in cancers, which spread by cells that multiply uncontrollably.

"There's a fine line between (the proper) response to injury and cancer," Mace said.

The idea that humans and insects share common genes is not far-fetched to scientists. Researchers have identified more than 2,200 genes in humans that are associated with disease – and 75 percent of those genes have counterparts in flies, said Ethan Bier, a UCSD biologist.

"Thirty percent of the genes are so similar that they're very likely to be functioning in exactly the same way," Bier said. "There's really a wide range of genes now that carry out similar functions in flies and humans."

The grainyhead gene, so critical to healing wounds in flies and humans, would have been life-saving for the ancestor the two creatures last shared 700 million years ago.

That animal, probably some type of shrimp or worm-like organism that swam in the primordial seas of Earth, would have relied on a "skin" that shielded it from a variety of threats.

And its grainyhead gene must have aided its survival as much as it helps human beings today – more than half a billion years later.

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