The classic fairy tale of Rapunzel tells the story of a prince who saves a maiden trapped in a tower by climbing up her long hair draped out the window. The secret behind Rapunzel’s cascading tresses is likely found in her healthy dermal papilla (DP) cells—a group of specialised skin cells in the base of hair follicles, that regulate hair growth.
DPs also control hair pigmentation, a feature that interests Krystle Joy Ng, a Research Fellow at the A*STAR Skin Research Labs (A*SRL). Humans produce two forms of a pigment molecule called melanin to confer hair colour: the black-toned eumelanin that provides sun protection and the reddish pheomelanin.
“Understanding the mechanisms regulating the type of pigment produced can provide insights into therapeutics for skin cancers like melanoma,” said Ng, adding that individuals with more pheomelanin are up to 40 times more prone to skin cancer.
The team led by Carlos Clavel, a Principal Investigator at the A*STAR Skin Research Labs (A*SRL), used a genetically engineered mouse model to study the genetics of melanin regulation by DPs.
In previous studies, Clavel’s team discovered that a gene called Sox2, which acts as a master regulator in DPs, influences several cellular processes involved in hair growth. Here, the team characterised the expression patterns of the leptin receptor (LepR) which allowed them to target and track Sox2 activity in DPs over the hair follicle growth cycle.
LepR’s unique capabilities made it highly valuable for demystifying the complexities of hair growth, said Clavel. “There was a need to improve the currently available tools for studying DPs,” he explained. “Most conventional approaches cannot specifically target the DP from the moment hair follicles develop to the hair cycle stages during adulthood.”
Using a genetic tool called Cre-Lox recombination, the team eliminated Sox2 in LepR-expressing mouse DPs, resulting in hair follicles producing lighter-coloured hair with less eumelanin and more pheomelanin. Additionally, they discovered that Sox2 regulates bone morphogenic protein (BMP) signalling, which controls the activity of pigment-producing melanocytes. Together, the team's findings showed that DP cells not only control the choice of hair pigment, but also the overall production of pigment in hair follicles.
How DPs and other cells surrounding hair follicles regulate hair pigmentation has, until now, remained unclear. With the help of innovative genetic tools such as Cre-Lox, it’s becoming easier to connect the dots between the molecular pathways that control hair and skin colours, providing exciting new avenues for targeted therapies to treat and prevent skin cancer.
Moving forward, Ng and Clavel plan to use a similar strategy to probe other pathways governed by Sox2. "We are now digging deeper into the molecular mechanism by which Sox2 controls melanogenesis in human skin,” Clavel concluded.
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Skin Research Labs (A*SRL).
