The path to her group's hair growth discovery began with a search for factors that determine how embryonic skin cells are able to choose between becoming epidermis or a hair follicle, says HHMI investigator Elaine Fuchs.
Photo: Mark Segal

Protein Spurs Hair Growth,
Sheds Light on Tumor Formation

You could call it a hair-raising discovery. A research team led by Elaine Fuchs, a Howard Hughes Medical Institute investigator at the University of Chicago, has for the first time induced new hair follicles to form in mature mammals. These surprising findings, achieved in mice, suggest that the protein ß-catenin may be a long-sought signal that instructs embryonic skin cells to become hair follicles.

Fuchs' research, reported in the November 25, 1998, issue of the journal Cell, may be good news for the millions of men and women worldwide who have age-related hair loss or baldness. Scientists have long pursued cures for baldness, but with limited success, in part because there has been no way to coax the adult scalp to generate new hair follicles.

Fuchs' research team's findings offer more than a potential remedy for baldness, however. They give scientists a better understanding of how certain benign skin tumors form, and they may also suggest a way to create woollier sheep.

In mammalian embryos, skin begins as a single layer of epithelial cells that cover the surface of the embryo. Patterned developmental cues trigger some of these cells to form hair follicles, which appear as tiny pockets dotting the skin surface. As the follicles grow during development, they differentiate into distinct layers. At maturity—which occurs shortly after birth—the follicles consist of two sheaths surrounding the hair shaft, which is the portion of the hair that is visible to the eye.

Differentiating cells in an adult follicle produce the protein keratin, which forms intracellular fibers that harden within the dying cells that compose the budding hair shaft. As the follicle makes new hair cells, the shaft lengthens and pushes out through the skin surface, usually at a rate of about one centimeter a month. Hair growth is not constant, however, because follicles are 3cycling" through stages of growth, rest and regression. When a follicle is in regression, its hair shaft falls out, to be replaced by a new shaft when the follicle reenters the growth stage. Not all follicles cycle in synchrony. At any one time, 85 percent of a person's hair follicles produce hair while the others are in the resting or regressing stage.

Until now, researchers thought that hair follicles form only during embryonic development. This would mean that each individual is born with a fixed number of hair follicles. The average human head, for example, has about 100,000 hair follicles spread across the scalp. Each follicle in a developing embryo receives a reservoir of stem cells that are capable of differentiating to produce hairs. But that doesn't guarantee a lifetime of luxuriant hair growth. In some men and women, follicles shrink, or "miniaturize," with age, churning out shorter and fewer hairs. This can eventually lead to inactivation of the hair follicles and subsequent hair loss. In male and female pattern baldness, or androgenic alopecia, a combination of genetic and hormonal alterations can elicit this response.

Men with androgenic alopecia might begin to notice hair loss as early as their teens. The thinning tends to follow a characteristic pattern: the hairline recedes first from the forehead and temples and then from the crown of the head. Women are usually in their forties or older before any permanent hair loss begins, and the thinning is much more diffuse than in men. Scientists aren't sure exactly why some people's hair follicles miniaturize, but they suspect a genetic influence because androgenic alopecia runs in families.

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Reprinted from the June 1999 HHMI Bulletin,Vol. 12,
No.2, pp 6-9. To subscribe...

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