The Walking Dead: sequential nuclear and organelle destruction during hair development

Abstract

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 following immunohistochemical staining.

Results

A focal point of respiratory activity was evident in keratogenous zone cells within the hair shaft that also exhibited nuclear damage. Nuclear degradation occurred via both caspase-dependant and -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 ROS 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.

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