Heady research: Study finds molecule triggers hair growth in mouse embryos

Comb-overs might not be the only solution for those who are losing their hair. A molecule that prompts hair follicle development in utero might one day be used to treat hair loss or combat excess hair growth.

Scientists at the School of Medicine used genetically engineered mouse embryos to demonstrate that the molecule, called laminin-511, signals embryonic stem cells in the skin to start growing hair. The signal may also prompt development of other organs and limbs.

'Now we have a signal protein that can support the microenvironment for hair development, and maybe also for hair renewal,' said Jing Gao, MD, a postdoctoral scholar in epithelial biology. Gao is the lead author of a paper describing the finding that was published in the Aug. 1 issue of Genes & Development.

Early in mammalian development, laminin-511 sets up a conversation between stem cells in the two outer layers of the skin. The top layer, the epidermis, is separated by an intracellular space from the skin layer below, called the dermis. Laminin-511 helps bridge the gap between the layers. The epidermis pumps out laminin-511, which crosses to the dermis and stimulates dermal cells to grow tiny, antennae-like projections that pick up epidermal signals.

'Laminin-511 acts at the crossroads between cell compartments, helping the cells communicate,' said the senior author of the study, Peter Marinkovich, MD, associate professor of dermatology and a member of the Stanford Cancer Center. 'It works through antennae called primary cilia.'

In addition to spurring formation of primary cilia, laminin-511 triggers a chain reaction of biological signals that travel back and forth between the dermis and the epidermis. The signals, which are sensed by the primary cilia, start hair follicles growing in the dermis.

Laminin-511 made hair grow at a specific stage of embryonic development in mice, equivalent to about the eighth month in human pregnancy, but the researchers are hopeful it might work later in life, too. They'd like to put their findings to work against hair loss.

'There are a lot of different causes of hair loss,' Marinkovich said. Further research will test if any forms of hair loss are influenced by laminin-511, he said.

'Injecting laminin-511 into the skin might, under some circumstances, promote hair growth,' he added.

If laminin-511 triggers hair growth after birth, Marinkovich expects it could used as a drug. Because the molecule acts between skin layers, rather than inside a cell, it could be injected into the skin area where hair was lacking.

Cancer chemotherapy patients might be good candidates for testing laminin-511's ability to regenerate hair, Marinkovich said. Sonic hedgehog, a signal protein that the study showed was activated by laminin-511, has some ability to encourage hair regrowth in chemotherapy patients. That could be a hint that laminin-511 might help reverse chemotherapy hair loss.

In addition, injecting antibodies against laminin-511 might be a way to block hair growth, providing a potential alternative to current treatments such as laser hair removal.

To deduce how hair follicles form, Gao compared skin from normal mouse embryos to skin from mouse embryos genetically engineered to be deficient in laminin-511. She observed changes in gene activity and skin structure as embryonic development progressed.

Gao also developed a new assay, soaking pieces of skin in baths of signal molecules to check which signals made hair grow. The new technique, which Marinkovich characterized as 'elegant and simple,' has already garnered attention from other scientists who study hair growth. 'The hair researchers were quite surprised with this assay,' Marinkovich said, noting Gao's method is much easier than the genetic techniques typically used to examine skin development.

Gao and Marinkovich say their work has implications beyond explaining how hair follicles mature.

'Our finding that laminin-511 stimulates primary cilia formation was pretty surprising,' Gao said. Primary cilia, the cellular 'antennae' she observed, also help drive formation of the kidneys, craniofacial structures and limbs.

At Stanford, Marinkovich and Gao collaborated with Mindy DeRouen, a doctoral student in dermatology; lab assistants Chih-Hsin Chen, MS, and Ngon Nguyen; Michael Nguyen, undergraduate student, and Anthony Oro, MD, PhD, associate professor of dermatology and member of the Stanford Cancer Center. The team included scientists at Harvard Medical School, Osaka University in Japan and Washington University School of Medicine in St. Louis.

The research was supported by two grants from the National Institutes of Health.

Erin Digitale is a science-writing intern in the Office of Communication & Public Affairs.