New follicle growth

Substance discovered that induces hair follicle formation in the mature skin cells of mice

November 25, 1998

Everyone has bad hair days. For 30 million men in the United States, roughly 40 percent of those over 35, every day is a no hair day. The good news is that thanks to new research, baldness may be fading away.

Researchers from the Howard Hughes Institute at the University of Chicago have induced hair follicle formation in the mature skin cells of mice. Follicle formation is a once-in-a-lifetime event that ordinarily happens only during early embryogenesis.

Their findings, reported in the November 25, 1998 issue of Cell, indicate that a molecule called beta-catenin may be the long sought message that instructs embryonic cells to become hair follicles, suggesting possible treatments for premature baldness.

"Beta-catenin can cause adult epithelial cells to revert to an embryonic-like state where they have the ability to choose to become a hair follicle," says Elaine Fuchs, Amgen Professor in the departments of molecular genetics and cell biology, Howard Hughes Investigator, and lead author of the paper. "This is exciting, because current treatments for baldness only work if there are living follicles left or if the patient undergoes hair transplant surgery. Our research shows that new follicles can be created from adult skin cells if certain molecular players are induced to act."

Beta-catenin performs two very different functions. In adult epithelial cells, it participates in binding neighboring cells together to facilitate cell-cell communication. But during embryogenesis, beta-catenin appears to have another role: it reacts with a molecule called LEF-1, which is expressed only in cells that will eventually become hair follicles. Together, beta-catenin and LEF-1 form a transcription factor that binds to the cell's DNA and activates the genes that instruct the cell to become a hair follicle.

Uri Gat, a postdoctoral fellow in Fuchs's lab, created mice that constantly produced a stabilized form of beta-catenin in their skin. (Normally any excess beta-catenin that is not needed for cell-cell adhesion is quickly degraded.) "The process caused some epidermal cells to make the partner molecule, LEF-1," explains Fuchs. "Wherever both stabilized beta-catenin and LEF-1 were present in an epithelial cell, a new hair follicle formed. If we can induce those two partners at the right time, new hair could be formed in places where it has been lost."

The genetically engineered mice were exceptionally hairy. In some mice, most skin cells became hair follicles. Unlike in embryogenesis, however, the genetically engineered skin of the transgenic mice made an endless supply of beta-catenin and benign follicle tumors formed.

"This is a case of too much of a good thing leading to a bad thing," says Fuchs. She cautions that the use of these exciting findings will still need more work before hair growth can be induced without danger of unwanted side-effects.

"If we can find a way to transiently express beta-catenin in these skin cells--just until new follicles are established--and then turn it off, we may be able to prevent tumor formation and still allow hair follicles to form," says Fuchs. The flip side of this, she says, is that it is also a potential tool to stop unwanted hair growth by inhibiting the pathway.

It could also have applications in the agricultural industry--for example to engineer sheep with denser wool or thicker skin, Fuchs explains.

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