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Hair tomorrow?

It’s likely that many of the 30 million balding men in the United States—roughly 40 percent of those over age 35—would do just about anything for a bad-hair day. Providing a strand of hope for these men, Chicago researchers have discovered a way to stimulate the growthof hair follicles. One day, their technique may safely reverse balding.

Ordinarily, hair-follicle formation is a once-in-a-lifetime event, occurring as the fetus develops in the womb. A lack of understanding of how hair follicles form has been a major block to the development of new and improved hair-loss therapies.
Now—led by Elaine Fuchs, the Amgen professor in the departments of molecular genetics and cell biology—a research team from the University’s Howard Hughes Medical Institute has made hair follicles form in the mature skin cells of mice. The team’s findings, reported in the November 25 issue of Cell, indicate that the molecule beta-catenin, along with its associated partner proteins, may be the long-sought messenger that instructs embryonic cells to become hair follicles.

“This is exciting because current treatments for baldness only work if there are living follicles left, or if the patient undergoes hair transplant surgery,” explains Fuchs. “Our research shows that new follicles can be created from adult skin cells if certain molecular players are induced to act.”

Most of the embryonic cells have the capability to become a variety of cells. They ultimately become a particular type of cell based on tiny differences in the concentration of a few chemicals and molecules in their immediate vicinity. While beta-catenin is used at all times to hold skin cells together, before birth it can also accumulate at higher levels in some skin cells and interact with another molecule called LEF-1. When LEF-1 and beta-catenin join together in the same skin cell, that cell becomes a hair follicle.

The team made this discovery not in a quest for a cure for baldness, but while conducting research into the general biology of how skin proteins work. When they pursued the special function of beta-catenin, they realized its potential clinical applications.
Postdoctoral fellow Uri Gat worked with graduate student Ramanuj DasGupta and senior research specialist Linda Degenstein, AB’77, to genetically engineer adult mice that produced an endless supply of beta-catenin in their skin, causing their skin cells to revert to embryonic cells capable of hair-follicle formation. “It is amazing,” says Fuchs, “that this single genetic change can cause an adult epidermal cell to become more like a fetal skin cell, able to be either an epidermal or a hair-follicle cell.”

Fuchs cautions that hair-follicle formation will require more study before hair growth can be induced without unwanted side effects. Like many growth-promoting factors, she explains, unchecked levels of beta-catenin can lead to the development of tumors. In the engineered mice, benign tumors grew in hair follicles as a result of excess beta-catenin—normal mouse skin cells destroy beta-catenin that is not immediately used. “This is a case of too much of a good thing leading to a bad thing,” she says.

If researchers can find a way to induce beta-catenin in skin cells just until new follicles have formed and then turn it off, Fuchs suggests, tumor formation may be prevented while hair follicles are still allowed to develop—offering a potentially more effective option for reversing baldness than topical hair-growth medications or hair transplantation.—Sharon Parmet

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