From Living Cells to Strong Strands
In this article you will learn about the process of cornification in hair follicles, where hair shaft keratinocytes transition from living cells to structural cells lacking a nucleus or cytoplasm. The study investigates this by analyzing scalp biopsies and hair-pluck samples, revealing that nuclear degradation occurs via caspase-dependent and independent pathways. Bnip3L-driven mitophagy plays a role in removing mitochondria, completing the transition from living to dead cells, crucial for forming strong hair fibers.
L.A. Jones, D.P. Harland, B.B. Jarrold, J.E. Connolly, M.G. Davis
The walking dead: sequential nuclear and organelle destruction during hair development
BACKGROUND
The transition of hair shaft keratinocytes from living, nucleated cells to structural cells without a nucleus or cytoplasm is essential for hair production. This process, known as cornification, requires the removal of cellular organelles to allow the cytoplasm to pack with keratin filament bundles, which then cross-link to form a strong hair fiber. While well-understood in epidermal keratinocytes, the mechanisms in hair follicles are not as clear.
OBJECTIVE
To gain insights into the mechanisms of cornification within the hair follicle to improve our understanding of normal hair physiology.
METHOD
The study obtained scalp biopsies and hair-pluck samples from healthy human donors. These samples were then analyzed microscopically after immunohistochemical staining. Confocal microscopy was used to capture fluorescent images, and transmission electron microscopy was used for ultrastructural analysis. Various markers were used to assess proliferation, mitochondrial presence, DNA fragmentation, apoptosis, and autophagy.
RESULTS
Evidence of respiratory activity and nuclear damage in keratogenous zone cells was found within the hair shaft. Nuclear degradation occurred through both caspase-dependent and caspase-independent pathways. Mitophagy, the removal of mitochondria, was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson's Fringe.
CONCLUSION
There is a stepwise living-dead transition in hair formation. Functional, nucleated cells degrade nuclear DNA but continue to respire and provide reactive oxygen species for keratin cross-linking. Eventually, Bnip3L expression triggers mitophagy, removing the last living characteristics, completing the transition from living to dead.
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CONFLICT OF INTEREST STATEMENT
This work was co-funded by Procter and Gamble and Agency for Science, Technology and Research, Singapore