Discovery could lead to treatments for baldnessBy Sharon Parmet
Medical Center Public Affairs
For roughly 40 percent of U.S. men over age 35, premature baldness remains a largely incurable condition. Researchers at the Universitys Howard Hughes Institute may have good news for these menpotential hair-loss treatments based upon hair follicle formation.
Hair follicle formation is ordinarily a once-in-a-lifetime event that occurs during development in the womb. However, Chicago researchers have been able to induce follicle formation in the mature skin cells of mice.
The researchers findings, reported in todays issue of Cell, indicate that a molecule called beta-catenin operating with its associated partner proteins may be the long-sought message that instructs embryonic cells to become hair follicles. This information is an important first step in understanding the key to hair follicle formation, and the work has implications for the future development of possible treatments for premature baldness.
The stabilization of beta-catenin in adult skin cells appears to enable these cells to revert to an embryonic-like state, where they have the ability to choose to become a hair follicle, said Elaine Fuchs, Amgen Professor in Molecular Genetics & Cell Biology, Howard Hughes Investigator and lead author of the research article. This is exciting because current treatments for baldness only work if there are living follicles left, or if the patient undergoes hair transplant surgery. Our research shows that new follicles can be created from adult skin cells if certain molecular players are induced to act.
At all times, beta-catenin is used at cell-cell junctions to hold skin cells together. But before birth, beta-catenin can also accumulate at higher levels in some skin cells, where it then interacts with another molecule called LEF-1. These embryonic skin cells are the ones that will one day become hair follicles.
Most embryonic cells have the capability to become different types of cells. They choose which cell type to become based on tiny differences in the concentration of a few chemicals and molecules in their immediate vicinity. When LEF-1 and beta-catenin join together in the same cell, that cell becomes a hair follicle.
Uri Gat, a postdoctoral fellow in Fuchs lab, genetically engineered mice that expressed both beta-catenin and LEF-1 in their skin cells. These mice were exceptionally hairy. In some mice, most of the skin cells became hair follicles.
But because the engineered mice produced an endless supply of beta-catenin, hair follicle tumors eventually formed. In normal mouse skin cells, beta-catenin that is not immediately used is destroyed by the cell.
This is a case of too much of a good thing leading to a bad thing, said Fuchs. She cautions that hair follicle formation will require more work before hair growth can be induced without the danger of unwanted side effects.
Like many growth-promoting factors, deregulation of beta-catenin can lead to tumorigenesis. If we can find a way to transiently express beta-catenin in these skin cells just until new follicles are established and then turn it off, we may be able to prevent tumor formation and still allow hair follicles to form, said Fuchs.
The flip side, Fuchs explained, is that these findings potentially could be used as a tool to stop unwanted hair growth as well. They could also have applications in the agricultural industry; for example, sheep with denser wool or thicker skin could be genetically engineered.