Pigs and grizzlies, not monkeys, hold clues to youthful human skin

PULLMAN, Wash. - The secret to youthful appearance and repairing scars may lie in a microscopic skin structure humans share with pigs and grizzly bears - but, surprisingly, not monkeys.

While it had been thought these ridge and valley-like skin microstructures - called rete ridges - form during fetal growth, researchers at Washington State University's College of Veterinary Medicine found they actually develop shortly after birth and identified a key molecular signal that drives their development.

The findings, published in the journal Nature, could lead to new therapies designed to reverse or slow skin aging and improve wound and scar repair.

"These structures degrade as we age; now we know how they form and have a blueprint to guide future work on restoring them," said Ryan Driskell, an associate professor in the College of Veterinary Medicine's School of Molecular Biosciences and senior author on the paper. "Most scientists assumed these skin ridges formed during early embryonic development, which explains why no one really understood their origin."

Rete ridges act like biological "Velcro," Driskell said, anchoring the outer layer of skin, or epidermis, to the dermal layer beneath while helping to maintain elasticity and strength. As these ridges flatten with age, skin becomes thinner and more prone to sagging and damage.

Despite their importance, research has been stalled for decades by a major hurdle: the wrong animal models.

"When most people look at the skin of different animals, they see differences in fur. Rete ridges lie under the surface of skin, however, so it wasn't until we looked closer that we discovered that animals with thicker skin, like pigs, grizzly bears and dolphins, have rete ridges like we do," said Sean Thompson, a doctoral student in Driskell's lab who served as first author on the study. "In contrast, common biomedical models for humans like mice and non-human primates are furry and lack rete ridges."

While the grizzly bear provided evolutionary data that suggests body size dictates skin structure, the bear's unique biology made it impossible to track day-by-day development of rete ridges. This led the team to the pig, which has a developmental timeline that researchers could precisely monitor.

Partnering with local farmers, the team collected skin tissue samples from pigs at various developmental stages and ultimately showed that rete ridges form after birth.

"We expected this structure to be established before birth, so seeing it emerge afterward was a surprise," Driskell said. "That timing changes how we think skin architecture is built and why it may be possible to influence it later in life."

Using advanced genetic mapping techniques, the team also identified a key biological pathway - bone morphogenetic protein (BMP) signaling - that activates to form these structures. This pathway serves as a set of molecular instructions, guiding how cells communicate and organize into complex tissue. Since rete ridges disappear with age, reactivating BMP signaling could help restore youthful skin and improve scar repair, in addition to possibly leading to new treatments for conditions like psoriasis.

"That BMP signaling drives rete ridges is exciting as it holds significant translational potential," said Maksim Plikus, a professor at the University of California, Irvine and co-author on the paper. "Use of BMP proteins has already been FDA-approved for orthodontic applications, mapping the way for their use in aged skin and scars."

The discovery also has the potential to help improve livestock health and adaptability to different climates. By understanding how these features form, researchers can explore ways to breed pigs and other livestock with skin traits suited for different conditions.

Driskell has filed a provisional patent related to his team's discoveries.

The study involved WSU's Bear Research, Education and Conservation Center and partnerships with local farmers and producers, with additional contributions from the University of Washington Birth Defects Research Laboratory and clinical collaborators at Spokane Dermatology. It was supported by the National Institutes of Health and the USDA Agricultural Research Service through the Resilient Livestock Initiative.

Media Contacts

• Ryan Driskell, WSU School of Molecular Biosciences, 509-338-8965, [email protected]
• Devin Rokyta, WSU College of Veterinary Medicine communications, 509-335-1911, [email protected]