Hair today, gone tomorrow? Teasing out details of hair growth

Science News, Oct 20, 2001 by Damaris Christensen

So far, however, no malignancy has been observed in the mice treated with PTHrP blocker, Holick reports.

Although PTHrP is intriguing, it's not the only compound involved in the regular cycling of hair follicles. For example, without a compound known as beta-catenin, the progenitors of the keratin-producing cells can't specialize, George Cotsarelis, a dermatologist at the University of Pennsylvania School of Medicine in Philadelphia, and his colleagues reported in the May 18 CELL. A strain of mice that lacks this compound never grows hair.

Other researchers are exploring a family of proteins known as Wnts, which was originally identified in studies of development in the Drosophila fruit fly (SN: 7/7/01, p. 13). Hair follicles grown in laboratory dishes require these proteins to keep growing as they do in anagen, say Bruce A. Morgan and his colleagues at Harvard Medical School in Boston.

Elaine Fuchs of the Howard Hughes Medical Institute at the University of Chicago and her colleagues had previously demonstrated a role for Wnts and beta-catenin in the initial growth and development of hair follicles in embryos. It's as if the layers of embryonic cells need to "carry on a telephone conversation [to develop into a hair follicle], and the wires carrying the message are Wnt signals," Fuchs says.

She's shown that Wnts bind to specialized receptors on a cell's surface, thereby preventing proteins inside the cell from breaking down beta-catenin. This compound then joins with other molecules to activate specific genes. The proteins that they encode cause the cells to initiate hair formation--for example, by producing keratin.

Further evidence for the importance of the Wnt pathway emerged when Fuchs' group created genetically engineered mice that couldn't degrade betacatenin. This essentially made the cells behave as though they were constantly bombarded with Wnt signals. These mice developed new hair follicles as adults and so sported lush coats. As the mice aged, however, they also developed benign lumps resembling human scalp tumors.

Fuchs and her colleagues have altered different factors in the Wnt signaling pathways to coax precursor cells in hair follicles to specialize into either skin cells or the cells that make up the hair follicle and a nearby gland. The researchers described these findings in the July 1 GENES AND DEVELOPMENT. The implication, Fuchs says, is that Wnts play an important role in hair cycling, as well as in the development of hair follicles.

The same caution must be applied to potential treatments based on Wnts and beta-catenin as to those based on PTHrP. Animal studies have linked Wnts and abnormal amounts of betacatenin to the growth of malignant tumors of the colon, liver, breast, and reproductive tract.

To develop treatments for hair disorders while minimizing cancer risk, Fuchs suggests supplying Wnts in a pattern that mimics nature's precisely controlled delivery. Alternatively, effective treatments might come from interfering with steps in the Wnt cascade other than beta-catenin.