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The walking dead: Sequential nuclear and organelle destruction during hair development

journal contribution
posted on 2023-05-03, 12:47 authored by Leigh Jones, Duane HarlandDuane Harland, Bradley Jarrold, John Connolly, Michael Davis
Background: Transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. This form of cell ‘death’, or cornification, requires cellular organelle removal to allow the cytoplasm to become packed with keratin filament bundles that further require cross-linking to create a strong hair fibre. Although these processes are well described in epidermal keratinocytes, there is a lack of understanding of such mechanisms, specifically in the hair follicle. Objectives: To gain insights into cornification mechanisms within the hair follicle and thus improve our understanding of normal hair physiology. Methods: Scalp biopsies and hair-pluck samples were obtained from healthy human donors and analysed microscopically after immunohistochemical staining. Results: A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft, which also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependent and caspase-independent pathways. Conversely, mitophagy was driven by Bnip3L and restricted to the boundary of the keratogenous zone at Adamson’s Fringe. Conclusions: We propose a model of stepwise living–dead transition within the first 1 mm of hair formation, whereby fully functional, nucleated cells first consolidate required functions by degrading nuclear DNA, yet continue to respire and provide the source of reactive oxygen species required for keratin cross-linking. Finally, as the cells become packed with keratin bundles, Bnip3L expression triggers mitophagy to rid the cells of the last remaining ‘living’ characteristic, thus completing the march from ‘living’ to ‘dead’ within the hair follicle.


Rights statement

© 2017 British Association of Dermatologists


  • English

Does this contain Māori information or data?

  • No



Journal title

British Journal of Dermatology




Jones, L. A., Harland, D. P., Jarrold, B. B., Connolly, J. E., & Davis, M. G. (2018). The walking dead: sequential nuclear and organelle destruction during hair development. British Journal of Dermatology, 178(6), 1341–1352. doi:10.1111/bjd.16148

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