By Lidia Wasowicz
UPI Senior Science Writer

In a solution to a hairy puzzle that might be at the root of conditions ranging from baldness to cancer, Rockefeller University scientists in New York City have traced the path by which skin turns to hair.

The results of the mouse experiments could point to ways of controlling the amount and location of human hair growth, as well as managing a variety of ailments, including the potentially deadly squamous cell carcinoma of the skin common among sun-worshippers, the investigators said. Their findings will be published in the March 20 issue of the British journal Nature.

In revealing the long-sought genetic trigger that can spell the difference between luxuriant locks and beaming baldness, the researchers described three necessary steps for transforming skin cells into hair follicles.

To start the process, the team reported, a skin precursor cell, called a stem cell, must receive signals from two proteins previously thought to have no connection to each other.

It turns out, however, the dynamic duo works hand-in-hand to activate hair-raising elements in the cell's center. These, in turn, lower the levels of a sticky molecule called E-cadherin, which acts as the glue that binds the cells into a tightly knit community,

With E-cadherin's hold eased, the cells can break free of their neighbors and -- in a move essential for hair growth -- shift their position. This rearrangement allows a "pit" to form in the skin and, in the final step, a hair follicle to develop.

E-cadherin can cut both ways, however. Too much of the protein and hair cannot develop; too little and cancer might result, said study first author Colin Jamora, of the Laboratory of Mammalian Cell Biology and Development at Rockefeller's Howard Hughes Medical Institute.

"Many laboratories, including my own, have focused on deciphering the complex steps required for the formation of hair follicles in the skin," Elaine Fuchs, HHMI investigator, professor and laboratory head, told United Press International.

"During embryonic development, a single layer of skin stem cells produces the hair follicles and the epidermis of the skin," she explained. "In order to make a hair follicle, cells in this single layer of stem cells must loosen their contacts with their neighbors and grow downward, changing their shape and their interactions during this movement, as well as beginning to express the genes that enable them to form hair."

A parallel process might underline the creation of other organs, such as teeth, lungs and limbs.

The hair-splitting study reveals minute details of mechanisms that determine a precursor cell's destiny, scientists told UPI.

"It's often difficult to tell when two people are siblings -- despite their common origins and upbringing, they are usually very different," said Dr. Yann Barrandon of the School of Life Sciences at the Swiss Federal Institute of Technology in Lausanne. "Similarly, it is not always obvious when distinct cell types have been produced from the same precursor cells."

Amazingly, mammary glands, sweat glands and hair follicles all arise from the same batch of stem cells piled atop the "primitive epidermis," an embryo's outermost cell layer, noted Barrandon, a member of the Department of Experimental Surgery at Vaud University Hospital in Lausanne, who analyzed the study in an accompanying commentary.

The mouse studies revealed two proteins, called Wnt and noggin, work in concert to determine the fate of a cell genetically programmed to develop either into hair or skin. Because the pair occurs naturally in humans, the finding could lead to medical applications, researchers said.

Already, they have linked glitches in the course Wnt follows in hair growth to the spread of colon, breast, skin and some other cancers.

In dissecting the series of steps leading to a stem cell leaving its Hair Loss turf, scientists could gain insights into how a malignancy spreads from the host tumor to other parts of the body in an often-lethal process called metastasis, Fuchs said.

The study adds to a growing body of evidence surrounding cell parts known as adherens junctions. Once thought useful only as the glue holding tissue cells together, adherens junctions actually serve a meatier role. They help to control an all-important switch that starts or stops genes carrying an organism's inheritance instructions, researchers noted.

The silence of the genes -- or their activity -- can have life-transforming effects. For example, a trigger gone haywire can turn a cell precisely calibrated to promote health and vigor into a runaway purveyor of destruction and death.

"The reason why tumor cells don't interact properly with other cells may be that their levels of adherens junction proteins are not maintained," Fuchs speculated. "For example, squamous cell skin cancers are large masses of cells that (fold) downward."

The research also might give scientists a heads-up on a less serious but more common condition -- baldness.

"We identified a possible therapeutic modality to address issues of hair growth," Fuchs told UPI. "Wnts and noggins are natural factors that are made by the skin. We have shown that noggins and Wnts can be topically applied to skin stem cells in culture to stimulate them into taking the very first steps in making a hair follicle."

She called this an important step toward the goal of laboratory-controlled production of hair and skin.

"Skin turns over every two weeks, so there is an enormous reservoir of stem cells there," Fuchs noted. "(Conversely), a knowledge of the factors that naturally induce hair follicle formation should be useful in designing new treatments for blocking these factors, and hence inhibiting hair growth in unwanted places."

Although male-patterned baldness -- responsible for some 95 percent of all hair loss in men -- is due primarily to hormones that disrupt the natural hair cycle of death and growth, some elements described in the new study also could be implicated, researchers said.

The work identifies external signals, naturally present in developing skin, which stimulate the production of hair follicles, they said.

"Before this, we didn't know how multiple growth factors collaborated to cause changes within the cell," Jamora said. "Now we know how two of the known ones target a specific gene to change the cell's function."

The researchers think some form of the mechanism they uncovered is present in other species.

"Avian feathers, for instance, are likely to be under similar regulation to the hair," Jamora told UPI. "It is both interesting and remarkable that defects in the Wnt pathway were first discovered in fruit flies, which exhibited abnormalities in wings and in body hairs."

The scientists will continue to explore processes underlying the formation of hair follicles, in hopes of gaining insights into the molecular misdeeds that result in disease, Fuchs said.

"Nature has clearly had more fun and fancy in creating body surfaces than she has in generating any of the other organs of our body. As humans, we too have been fascinated by our skin, and nearly all societies have worked to further adorn what nature has given us," Fuchs commented.

"Research scientists are just beginning to unlock the mysteries underlying the biology of skin and hair," she concluded. "It is our hope that in time, this information will help in developing new technologies for regulating hair growth and for replacing skin and hair damaged in injury. In addition, we hope to use this information to uncover the underlying bases of the myriad of skin disorders, including many types of skin cancers, whose genetic abnormalities remain unknown."

The study was funded by the National Institutes of Health and the Howard Hughes Medical Institute.