Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin

Nakafusa, Jyunji; Narisawa, Yutaka; Shinogi, Taro; Taira, Kaoru; Tanaka, Tatsurou; Inoue, Takuya; Misago, Noriyuki

doi:10.1111/j.1365-2133.2006.07441.x

Cited by 28 publications

(35 citation statements)

References 38 publications

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“…Mature Merkel cells are post-mitotic (Moll et al, 1995), but quantitative, morphological and fate-mapping studies suggest that Merkel cells turnover throughout an organism's lifespan (Doucet et al, 2013;Moll et al, 1996;Nafstad, 1987;Nakafusa et al, 2006;Van Keymeulen et al, 2009). These data imply the existence of a Merkel cell precursor that gives rise to new Merkel cells.…”

Section: Discussionmentioning

confidence: 81%

“…At P0, the majority of K8+ cells co-expressed K18 and K20, and also took up FM1-43 ( Fig. 5A-C‴ Previous reports suggested that Merkel cell numbers in rodent hairy skin change during the hair cycle (Moll et al, 1996;Nakafusa et al, 2006), so we wondered whether hair cycle stage might affect competency of keratinocytes to respond to Atoh1 induction. Atoh1 induction for 24 h at P24-25 during anagen I followed by tissue harvest 4 days or 2 weeks later resulted in production of ∼55× (P=0.011, t-test) and ∼100× (P=0.004, t-test) more ectopic K8+ cells, respectively, than induction at P19-20 during telogen I (Fig.…”

Section: Atoh1mentioning

confidence: 99%

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EctopicAtoh1expression drives Merkel cell production in embryonic, postnatal and adult epidermis

et al. 2015

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Merkel cells are mechanosensitive skin cells whose production requires the basic helix-loop-helix transcription factor Atoh1. We induced ectopic Atoh1 expression in the skin of transgenic mice to determine whether Atoh1 was sufficient to create additional Merkel cells. In embryos, ectopic Atoh1 expression drove ectopic expression of the Merkel cell marker keratin 8 (K8) throughout the epidermis. Epidermal Atoh1 induction in adolescent mice similarly drove widespread K8 expression in glabrous skin of the paws, but in the whisker pads and body skin ectopic K8+ cells were confined to hair follicles and absent from interfollicular regions. Ectopic K8+ cells acquired several characteristics of mature Merkel cells in a time frame similar to that seen during postnatal development of normal Merkel cells. Although ectopic K8+ cell numbers decreased over time, small numbers of these cells remained in deep regions of body skin hair follicles at 3 months post-induction. In adult mice, greater numbers of ectopic K8+ cells were created by Atoh1 induction during anagen versus telogen and following disruption of Notch signaling by conditional deletion of Rbpj in the epidermis. Our data demonstrate that Atoh1 expression is sufficient to produce new Merkel cells in the epidermis, that epidermal cell competency to respond to Atoh1 varies by skin location, developmental age and hair cycle stage, and that the Notch pathway plays a key role in limiting epidermal cell competency to respond to Atoh1 expression.

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Section: Discussionmentioning

confidence: 81%

Section: Atoh1mentioning

confidence: 99%

EctopicAtoh1expression drives Merkel cell production in embryonic, postnatal and adult epidermis

et al. 2015

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“…Together with the results found for NGF-R and N-CAM, these data suggest that most MCs in hair follicles are not involved in mechanoreception and are not associated with nerve Wbers. In this context, the presence of dendritic and round MCs in hair follicles (Nakafusa et al 2006) is striking. Moreover, a change of the number of dendritic MCs was observed during the hair cycle, while the amount of round MCs was not altered.…”

Section: Discussionmentioning

confidence: 96%

Evidence for distinct populations of human Merkel cells

Eispert

Fuchs

Brandner

et al. 2009

Histochem Cell Biol

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Merkel cells (MCs) are neuroendocrine cells of unknown origin located in the skin. They are identified at electron microscopic level by electron dense granules, at light microscopic level by the presence of cytokeratins 8, 18, 19 and 20. Contradictory reports concerning the presence of other molecules of epithelial as well as neural origin prompted us to investigate whether there are distinct populations of human MCs. Here, we show the heterogeneous expression of villin, N-CAM, NGF-R, and neurofilaments in MCs. Synaptophysin is found in all MCs but with different intensity, nestin is absent. Expression patterns vary between interfollicular epidermis, hair follicles and glabrous epidermis. We conclude that there are distinct populations of MCs, but all populations contain markers for epithelial as well as neural cells. Putative functions of the distinct populations are discussed.

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“…Touch dome keratinocytes have a distinct molecular profile compared with the surrounding epidermis, including expression of keratin 17 (K17) in basal cells (16). There is ongoing cellular turnover in touch domes, with constant production of stratified epithelial keratinocytes and cyclical expansion of terminally differentiated Merkel cells that coincides with anagen regeneration in the hair cycle (17). Genetic fate mapping has shown that the progenitors maintaining these two cell types are found among the K17 + cells in the touch dome (18), with unipotent atonal homolog 1 (Atoh1)-positive progenitors maintaining the Merkel cells (19).…”

mentioning

confidence: 99%

Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium

Xiao

Thoresen

Williams

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The touch dome is a highly patterned mechanosensory structure in the epidermis composed of specialized keratinocytes in juxtaposition with innervated Merkel cells. The touch dome epithelium is maintained by tissue-specific stem cells, but the signals that regulate the touch dome are not known. We identify touch dome stem cells that are unique among epidermal cells in their activated Hedgehog signaling and ability to maintain the touch dome as a distinct lineage compartment. Skin denervation reveals that renewal of touch dome stem cells requires a perineural microenvironment, and deleting Sonic hedgehog (Shh) in neurons or Smoothened in the epidermis demonstrates that Shh is an essential niche factor that maintains touch dome stem cells. Up-regulation of Hedgehog signaling results in neoplastic expansion of touch dome keratinocytes but no Merkel cell neoplasia. These findings demonstrate that nerve-derived Shh is a critical regulator of lineage-specific stem cells that maintain specialized sensory compartments in the epidermis.

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Changes in the number of Merkel cells with the hair cycle in hair discs on rat back skin

Abstract: This difference of the hair cycle dependency between oval and dendritic-type Merkel cells suggests some functional differences, such as a secretory function, related to the hair cycle.

Cited by 28 publications

References 38 publications

EctopicAtoh1expression drives Merkel cell production in embryonic, postnatal and adult epidermis

EctopicAtoh1expression drives Merkel cell production in embryonic, postnatal and adult epidermis

Evidence for distinct populations of human Merkel cells

Neural Hedgehog signaling maintains stem cell renewal in the sensory touch dome epithelium

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