Sarah Millar and her team at the Perelman School of Medicine at the University of Pennsylvania have exploited a known property of hair follicle stem cells to restart hair growth in laboratory animals.
The Wnt signaling pathway is an important regulator of hair follicle proliferation, but does not seem to be required for hair follicle survival. Wnt signaling in cells culminated in the activation of a protein called beta-catenin, which goes to the nucleus of the cell and causes changes in gene expression.
Millar and her colleagues disrupted Wnt signaling in laboratory animals by expressed an inhibitor called Dkk1 in hair follicles. Dkk1 expression prevented hair growth, and when the hair follicles were examined, they still had their stem cell populations, but these stem cells were dormant. Removal of Dkk1 resumed Wnt/beta-catenin signaling, and restored hair growth.
Interestingly, Millar’s group found Wnt activity in non-hairy regions of the skin, such as palms, soles of feet, and so on. Therefore, in order for Wnt signaling to induce hair growth, it must occur within specific cell types.
This work also has additional applications: skin tumors often show over-active beta-catenin. Removing beta-catenin could prevent the growth of skin tumors, just as removing beta-catenin in the skin of these mice prevented proliferation of any hair follicles. However, agents that can activate beta-cateinin in hair follicles could reactivate dormant hair follicles and induce new hair growth.
Finding ways to safely reactivating the Wnt pathway in particular cells in the skin is a major focus of Millar’s research group. Such work may lead to treatments for male pattern baldness.