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Division of Dermatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, JapanDivision of Microscopic Anatomy, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
The presence of tactile structures in human hairy skin was first reported by Pinkus in 1902. He discovered distinct epidermal disc-like structures with nerves and “Tastzellen” (i.e., Merkel cells) at the base of the epidermis, and named these structures “Haarscheiben” because of their close association with hair follicles. These structures were revisited by later investigators (
), whereas some other investigators showed that Merkel cells arise from the epidermal progenitor cells under control of the Atoh1 transcription factor (
). In the present study, we aimed at investigating the three-dimensional (3D) morphology of the human “Haarscheiben”, or touch domes, by the combined use of light microscopy (LM) and scanning electron microscopy (SEM).
Touch domes observed by LM in hematoxylin–eosin-stained sections were characterized by their slightly thickened epidermis with clear cells, delineated by thick epidermal ridges in the periphery (Figure 1a and b). Immunohistochemical study for keratin 20 (K20), showing Merkel cells, and protein gene product 9.5, which stains nerve fibers, revealed the presence of numerous Merkel cell-neurite complexes in the base of the touch dome epidermis (Figure 1c). 3D reconstruction of K20-immunostained serial sections clearly showed the overall shape of the touch dome (Figure 1d and e). When viewed from the dermal side, the dome was an oval concave area with Merkel cells in the epidermal base, bordered by a circumferential deep epidermal ridge. These results corresponded well with those obtained by previous investigators (e.g.,
Figure 1Light micrographs of a human touch dome. (a) Hematoxylin–eosin-stained section of touch domes (small arrows) bordered by peripheral thick epidermal ridges (arrowheads). *Hair follicle. (b) Closer view of the region framed in a. Arrows: clear cells. (c) Immunohistochemical study for keratin 20 (K20) (brown) and protein gene product 9.5 (PGP 9.5) (violet). K20-immunopositive Merkel cells are in contact with PGP 9.5-positive nerve terminals (arrows). (d) Samples of K20-immunostained serial sections used for three-dimensional (3D) reconstruction. (e) 3D reconstruction from 44 serial sections. K20-immunopositive Merkel cells (pale red) are identified on the epidermal base of the touch dome. Note a circumferential epidermal ridge (arrowheads). Bars: a, d=100μm; b, c=10μm; and e=500μm.
KOH treatment was then used to separate the epidermis from the dermis. The localization of Merkel cells in the touch dome was determined by direct comparison of LM and SEM images of KOH-treated/K20-immunostained tissues (Figure 2a and b). The base of Merkel cells appeared to be covered by neuronal components because of their continuity to the branch of unmyelinated fibers (Figure 2c and d). The number of Merkel cells ranged from 60 to 265 Merkel cells per touch dome (n=6, the 65-year-old cadaver), depending on the dome size. The density of Merkel cells in the touch dome was 608±142 Merkel cells per mm2 (mean±SD).
Figure 2Human touch domes viewed from the dermal side. (a, b) Whole-mount epidermal specimen immunostained for keratin 20, and observed by light microscopy and scanning electron microscopy (SEM). (c, d) Closer views of the framed areas in a and b. Portions of Merkel cells (numbered 1–11) appear covered with neuronal components because of their continuity with unmyelinated fibers (white arrowheads). (e, f) Touch domes (colored purple) observed by SEM. Note epidermal ridges (white arrows) dividing the dome into subcompartments. Thick arrow: duct of sweat gland. *Hair follicles. (g, h) Nerve fibers (white arrowheads) connect the neighboring Merkel cell–neurite complexes (white asterisks). Note nerve terminals (arrows in g) ending in the epidermis. S: Schwann cell body. Bars: a, b=100μm; c, d=10μm; e, f=100μm; and g, h=10μm.
Touch domes were further studied by SEM observation of the dermal side after KOH-collagenase treatment (Figure 2e–h and Supplementary Figure S1 online). Domes were determined as concave areas bordered by a thick epidermal ridge, and they were characterized by the accumulation of unmyelinated nerve fibers in the dermal region. The shape of the touch domes varied from round to irregular (Supplementary Figure S1 online). The epidermal ridges in the touch domes were generally shallow, but they sometimes appeared thicker in certain areas, as if dividing the domes into two or more subcompartments (Figure 2e). The sizes of the touch domes were 0.036±0.035mm2 (mean±SD), ranging from 0.002 to 0.130mm2 in our SEM images; the smallest dome was estimated to be 50 × 40μm2 and the largest 580 × 290μm2 (n=26). Although hair follicles were sometimes associated with touch domes, they were not in the center of the domes but were rather beside them (Figure 2e and Supplementary Figure S1 online). Some touch domes appeared completely independent from hair follicles (Figure 2f and Supplementary Figure S1 online). In the 26 touch domes (four individuals) analyzed in our SEM studies, 13 touch domes were associated with hair follicles and the other 13 domes were independent from hair follicles.
Our SEM analysis also revealed the arrangement of Merkel cell-nerve complexes in the touch domes (Figure 2g and h). Schwann cell bodies were seen as spherical swellings around nerve branches. Unmyelinated nerve terminals extended into the base of Merkel cells and often innervated more than two Merkel cells with one terminal. Some nerve terminals also ended in the epidermis after innervating one or two Merkel cells (Figure 2g).
used transmission electron microscopy to show that axon terminals attaching to Merkel cells did not connect directly with other Merkel cells. However, our SEM findings clearly demonstrated that nerve branches often innervated more than two Merkel cells with one terminal. A similar finding was recently reported in the touch dome in cat hairy skin (
) using confocal laser scanning microscopy. Thus, it is probable that terminal unmyelinated branches form some territories in the human touch domes by innervating multiple Merkel cells with en-passant endings.
The function of the touch dome has been studied by previous investigators. Iggo and colleagues carried out electron microscopic studies in combination with physiological recordings from touch domes in cats and primates, and demonstrated that the touch domes generated a localized, highly sensitive, and slowly adapting discharge by vertical surface pressure (
). These findings imply that the touch dome has an important role in mechanoreception in hairy skin. Previous studies showed that a tylotrich follicle is present in the center of the touch dome in mice, rats, and guinea pigs, suggesting that the dome detects pressure upon the guard hair in those animals (
). The present study, however, revealed that the human touch dome was rather independent from hair follicles, although they were sometimes located beside the touch dome. This finding suggests that human touch domes function as touch spots independent from the structure for detecting the pressure upon the hair.
The general consensus is that Merkel cells are connected by terminals from a single myelinated Aβ fiber (
demonstrated the presence of Aδ and C-fibers as well as Aβ fibers in the human touch dome. We also showed that nerve fibers innervating the touch dome mostly ended as Merkel cell-neurite complexes, but partly ended on the base of keratinocytes in this area. It is probable that the human touch dome exceeds simple mechanosensation and has an important role in complex sensation as a touch spot in human hairy skin.
ACKNOWLEDGMENTS
We thank the members in the Division of Microscopic Anatomy, Niigata University Graduate School of Medical and Dental Sciences, for their technical assistance and valuable discussions throughout the study.
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