Shaggy genes. Expressing the Hairless gene in some cells rescued mutant mice from the chill of baldness.

Follicles Reborn

Researchers have coaxed a bald breed of mice to become furry again. While it doesn't provide an easy cure for hair loss, the study does uncover a key component of the genetic wiring behind hair growth in both mice and men.

To maintain luxurious locks, follicles in the skin must be periodically replaced when hairs fall out. This requires the activation of progenitor keratinocyte (PK) cells that turn into new follicles. Researchers have not been able to untangle the molecular signals that coordinate this process, but they do know that a gene called Hairless seems to play a role. Mice with a mutation in the gene start life with a full coat of fur but never grow it back once it falls out. Researchers also know that a cellular pathway called the Wnt signaling pathway induces hair growth. But the connection between Hairless and Wnt has never been found.

To fit the puzzle together, a team led by Catherine Thompson, a molecular biologist at the Kennedy Krieger Institute and Johns Hopkins University School of Medicine in Baltimore, Maryland, started by tracking the expression of Hairless in healthy follicles. The researchers found the Hairless protein within the PK cells, but only during the pauses between spurts of hair growth. As soon as the follicles were regenerated and growing new hair, the protein disappeared. This suggested that Hairless might be an on-switch for PK cells.

The researchers confirmed this by engineering the Hairless mutant mice to express a working copy of the gene just in their PK cells. Far better than any comb-over, the Hairless-expressing PK cells kept the mice furry, even after their first hairs fell out. And what's more, the team found that in healthy PK cells, Hairless blocked the expression of one of the proteins that turns off Wnt signaling. This indicates that Hairless may stimulate follicle growth by keeping the Wnt pathway running, Thompson and colleagues report online this week in Proceedings of the National Academy of Sciences.

But don't throw your toupee away just yet. Thompson says the findings likely won't provide an easy cure for baldness because male pattern baldness has other causes, some of which are hormonal. Still, "understanding the mechanisms by which hair normally regrows is potentially useful for designing therapeutic agents," she says.

The study is significant, says Chen-Ming Fan, a molecular biologist at the Carnegie Institution in Baltimore, Maryland, because it provides "the first clue" to how the hair growth cycle is regulated. Next comes the question of what makes Hairless turn on and off during the cycle, he says.

Related sites
All about hair loss
Thompson's home page
Fan's home page