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Why do humans have hair on their arms and legs but not on the palms and soles of their feet? It is a fundamental question of human evolution that researchers at the Perelman School of Medicine at the University of Pennsylvania claim to have found in a new study. Their findings reveal the existence of a natural inhibitor secreted in hairless developing skin that blocks a signaling pathway, called the WNT pathway, that controls hair growth. Cell reports published the study today.
"We know that WNT signaling is crucial for the development of hair follicles, blocking it causes hairless skin and moving from hair formation to the formation of more hair," said Sarah E. Millar, author Principal of the study, Ph.D., Albert M. Kligman Professor of Dermatology and Director of the Penn Resource Center on Skin Biology and Diseases. "In this study, we showed that skin in hairless regions naturally produced an inhibitor that prevented the TNO from doing its job."
This natural inhibitor is Dickkopf 2 (DKK2), a protein found in some embryonic and adult tissues, where it plays a variety of roles. The researchers tested the plantar skin of mice – roughly the equivalent of the underside of the human wrist – and found that DKK2 was highly expressed. In addition, when they genetically removed DKK2, the hairs started to grow in this normally hairless region of the skin.
"It's important because it tells us that TND is still present in hairless regions, it's just stuck," Millar said.
Some mammals, such as rabbits and polar bears, naturally develop hair in their plantar skin. The Millar research group found that unlike mice, DKK2 is not expressed at high levels in rabbit plantar skin, which is why hair can develop there. These results suggest that the production of DKK2 in specific skin regions has been modified during evolution to allow the formation of different hairless or hairy skin patterns depending on the needs of the animal.
Hair follicles develop during the fetal life, but their production ceases after birth. As a result, hair follicles do not regrow after severe burns or extensive, deep wounds in the skin. Millar and his team are currently investigating whether secreted WNT inhibitors inhibit hair follicle development in these scenarios.
While some areas of the human body are naturally hairless, others become so because of various diseases. According to the American Academy of Dermatology, more than 80 million people in America suffer from androgenetic alopecia, also known as baldness in men or women. Genome-wide association studies have identified DKK2 as a potential candidate gene associated with this disease, suggesting that it is a potential therapeutic target.
"We hope that these lines of investigation will unveil new ways to improve wound healing and hair growth, and we plan to pursue these goals to move forward," said Millar. .
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