Molecular Secrets Behind “Zigzag” Hair Patterns Uncovered

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RIKEN researchers have discovered how biological rhythms influence hair growth in mice. This finding could pave the way for new anti-aging treatments in humans.

The sleep and menstrual cycles are two examples of the vast array of biological rhythms that underlie almost all biological processes. Because such biological rhythms play an essential role from an organism’s inception through its old age, it is crucial to understand how they work. But not much is known about how such periodic cycles are maintained after birth.

Hair follicles in mammals provide an interesting system to investigate biological rhythms because they are repeatedly regenerated during the hair cycling process.

A team led by Takashi Tsuji of the RIKEN Center for Biosystems Dynamics Research has investigated the molecular mechanisms responsible for the characteristic bending pattern observed in ‘zigzag hairs’. These hairs, found in the undercoat of mice, develop kinks every three days during the follicle maturation process.

Now the team has discovered a molecular rhythm responsible for this hair growth phenomenon.

Every three days there was a noticeable shift in the spatial arrangement of progenitor cells located at the base of developing zigzag follicles in relation to supporting cells. These interactions were accompanied by cyclic fluctuations in biochemical signals.

This discovery could have practical applications. “By artificially controlling these molecules, it may be possible to regulate biological rhythms and potentially prevent age-related hair changes,” says Tsuji. “This could lead to the development of new healthcare products.”

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Tsuji’s team investigated the interplay between two specialized cell types at the base of hair follicles in genetically engineered mice. They found that crosstalk between these cells orchestrates the three-day molecular rhythms in mouse fur, with synchronized changes in the behavior of both cell types occurring just before bends in the zigzag hairs develop.

The researchers also identified two genes associated with cell growth and survival that played a crucial role in mediating these recurring physiological changes.

To investigate the significance of these genes, the researchers turned them off in one experiment and artificially increased their expression levels in another experiment (Fig. 1). In both cases, the genetic manipulations disrupted the molecular rhythms, resulting in a deviation from the zigzag shape of the hairs.

The team next plans to look for similar rhythms in human hair development.

“Variations in hair curvature exist between individuals and different ethnicities, creating significant interest in understanding the underlying biological rhythm,” says Tsuji. “If we can unravel this puzzle, it could allow us to manipulate the morphology of human hair at will and potentially halt age-related changes.”

Reference: Takeo M, Toyoshima K ei, Fujimoto R, et al. Cyclic dermal micro-niche switching regulates the morphological infradian rhythm of mouse zigzag hair. Wet Common. 2023;14(1):4478. doi: 10.1038/s41467-023-39605-z

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