Cecilia Lee

Researchers at the Yale School of Medicine are investigating the formation of hair follicles and found two crucial signals involved in their development. 

Researchers have traditionally struggled to determine how exactly hair follicles form — largely due to the difficulty in locating cells and resolving the signals around cells’ path of differentiation into hair follicles, according to Peggy Myung, professor of dermatology and pathology at Yale School of Medicine. In order to combat hair loss other techniques have been developed, like the Therapeutic hair transplant and several proven hair loss prevention products. This does not been study in this field has been abandoned however. Myung, along with Rihao Qu GRD ’23, a doctoral student at Yale in the Computational Biology and Bioinformatics Department, said studying hair follicles is important for two main reasons.

“One is so that we can reprogram adult skin to form hair follicles to treat hair loss,” Myung explained. “A second thing is to have a better understanding of how other appendages, like teeth and nails, form … with the assumption that they have a common program of growth and differentiation.” People who are suffering from hair loss may consider a hair transplant procedure to improve their appearance.

In order to gain an understanding of just how hair follicles form, Qu developed a computational method that enabled him to track the path that a developing cell takes when becoming a hair follicle.

Qu broke down the idea of hair follicle development with a metaphor. He said to imagine that a cell is driving down a road and that there are many possibilities for the cell to make turns. There are signals along this road that dictate what turns the cell actually takes. The culmination of the cell’s turns brings it to its final destination.

However, researchers have faced many difficulties in researching this differentiation pathway.

“It is a very complicated story involving an interdisciplinary approach, the hardest part is probably combing through all the biological data and computational analysis and distilling everything down to a simple message,” wrote Yiqun Jiang GRD ’25, a doctoral student and author on this study.

In this case, the cell’s final destination is its terminal or end state. All of the signals along the road represent the chemical signals that influence a cell’s path of differentiation. Essentially, the signals tell the cell to become a hair follicle and guide it along the path of doing so. 

The terminal state for the cells involved in hair follicle formation is a dermal condensate. The dermal condensate cells build up to form a pore from which hair grows. These dermal condensates regulate hair follicle formation, and therefore hair growth.

The computational method developed by Qu enabled him to sort through all of the signals the cell is subjected to on its path to becoming a dermal condensate. He was able to discover what the most important signals were in the cell’s differentiation path: sonic hedgehog and WNT.

In order to verify that these signals are in fact most critical to hair follicle formation, Myung mutated the genes that encode the sonic hedgehog and WNT signals.

“We used some genetic prohibition experiments to generate two biological systems,” said Qu. “One [of these systems] is normal, the other one will have defects and the cells will not successfully get close to [becoming] a dermal condensate … We want to compare these two biological systems … to know what specific cell population is associated with dermal condensate genesis.”

When the genes for the sonic hedgehog and WNT signals were deactivated, the analyzed mice lacked hair growth, thus forming no dermal condensates. Therefore, the two signals are essential to hair follicle development.

When the genes for the sonic hedgehog and WNT signals were overexpressed, it was found that dermal condensates would form spontaneously without the need for other signals along the cell differentiation pathway. This demonstrated that these two signals are sufficient for the formulation of hair follicles. The researchers also found that the sonic hedgehog and WNT signals work hand-in-hand. They are codependent and work together in a very specific manner. 

“We were able to see the dermal condensate without the existence of the other external signals, so that proves that not only are these signals [sonic hedgehog and WNT] essential, but also sufficient in dermal condensate formation,” explained Qu.

Myung explained that the next steps for this research involve trying to grow these dermal condensates in vivo using the signals deemed important through this study. This will enable the test of drugs for hair growth and more. Jiang also emphasized that future research should focus on understanding exactly how the sonic hedgehog and WNT signals interact along the differentiation pathway.  

More than 80 percent of men and nearly 50 percent of women experience significant hair loss during their lifetime.