Gene Triggers New Hair in Adult Mice

In research that could one day suggest ways to combat baldness or curb excessive hair growth, scientists have created mice whose skin continues to sprout new hair follicles long after birth. However, proliferating cells within the follicles sometimes give rise to tumors as well.

 In mammals, birth of hair follicles normally occurs only in a growing embryo. "During development, you're given a set number of hair follicles for the rest of your life," says Elaine Fuchs of the Howard Hughes Medical Institute at the University of Chicago.

 In the mice genetically engineered by Fuchs and her colleagues, however, new follicles also start to emerge several weeks after birth and continue to do so throughout life. Supplementing the normal coat the mice were born with, the new hairs arise from skin cells in between the preexisting follicles or even spring forth from the original follicles.

 These unusually furry rodents highlight a previously unrecognized signaling pathway that can command adult skin cells to give rise to new hair follicles, says Fuchs. A key component of this pathway appears to be a protein called beta-catenin. Fuchs' group has been interested in beta-catenin because it interacts with Lef-1, a protein already implicated in the development of hair follicles. When beta-catenin attaches to Lef-1, the pair can travel to the nucleus of a cell and activate genes specific to hair cells.

 In adult animals, any free beta-catenin in a cell is destroyed quickly. Fuchs and her colleagues, however, created mice whose skin cells had a gene encoding a form of beta-catenin that resists degradation. In some skin cells, but not all, this added beta-catenin ignited the development of new follicles. The scientists suspect that some still mysterious signal, perhaps released by existing follicles or other nearby cells, determines why only certain cells react to the extra beta-catenin.

 The new hair growth in the mice was not fully normal, Fuchs' team reports in the Nov. 25 Cell. Hair follicles frequently weren't angled appropriately, so hairs emerging from them didn't break the skin but extended beneath it. There were so many of these misaligned follicles, notes Fuchs, that "the skin actually got thicker."

 Two types of hair-follicle tumors also plagued the mice. Fuchs suggests that the tumors arise because the added beta-catenin gene is constantly stimulating cells to grow. She notes that similar cancers create bulges under the skin of some people and, though invariably benign, can be disfiguring.

 While the new research offers the hope that physicians will learn to control the beta-catenin pathway with drugs or topical agents, and consequently learn to inhibit abnormal hair growth or cure baldness, investigators caution that such goals remain far off. "There's tremendous potential here, but there's an enormous amount of additional experiments that need to be done," says Fuchs.

 Researchers, for example, need to test whether temporarily activating the beta-catenin pathway can generate new follicles without prompting tumors. Scientists note that the added beta-catenin gene functions during the mouse's embryogenesis and may cause permanent changes in skin cells that make them amenable to follicle formation in adulthood.

"Ideally, you would like to turn on beta-catenin just in an adult and see if you have the same effect: production of hair follicles," says George Cotsarelis of the University of Pennsylvania Medical Center in Philadelphia.