Merkel Cells Are Postmitotic Cells of Neural Crest Origin
Chick/quail chimeras and double transgenic Wntl -cre/R26R mice, in which neural crest cells are permanently marked by expression of ß-galactosidase, are evidence that Merkel cells in Merkel nerve endings of birds and mammals are neural crest derivatives.
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Summary Chick/quail chimeras and double transgenic Wntl-cre/R26R mice, in which neural crest cells are permanently marked by expression of p-galactosidase, are evidence that Merkel cells in Merkel nerve endings of birds and mammals are neural crest derivatives. Like melanoblasts their precursors colonise the skin. Cytokeratin 8- and 18-positive Merkel cells in mouse whisker follicles are postmitotic cells. They are Ki 67-negative and their nuclei exhibit features of differentiated resting cells. In contrast, Merkel cell progenitors are likely to be proliferating cells. Simple cytokeratins are not suitable markers for their identification. Possible progenitors of Merkel cells that contain dense core granules can be identified using electron microscopy in the connective tissue surrounding the bulge region of the whisker follicle. Possible progenitors of Merkel cells in epidermis are Pgalactosidase-positive, but cytokeratin-negative. Verification of the Merkel cell precursor nature of these cells requires specific markers that will enable us to distinguish them from precursors of melanoblasts. Thus, the question of the location of proliferative Merkel cell progenitors remains open.
Introduction Merkel cells, which are localized in the skin ofvertebrates, are large, oval cells with an electron-clear cytoplasm. The vast majority of Merkel cells are in close association with a nerve terminal. Recent experimental evidence points to direct involvement of the Merkel cells in transducing mechanical stimuli to action potentials in the afferent nerve fibre (Senok and Baumann 1997; Tazaki and Suzuki K. I. Baumann et al. (eds.), The Merkel Cell © Springer-Verlag Berlin Heidelberg 2003
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1998; Halata et al. 2003; see Baumann and Senok, this Vol.). Merkel cells were originally described by Merkel (1875) in the skin of birds and mammals. The electron-microscopic features of Merkel cells in birds (Saxod 1978; Halata and Grim 1993) are similar to those in mammals (Halata 1970). The main difference between avian and mammalian Merkel cells is their location. In mammals, Merkel cells are found in the basal layer of the epidermis (Munger 1965) and in the outer root sheath of the hair follicle, in particular in whiskers (Andres 1966). By contrast, Merkel cells in birds are localised in the dermal connective tissue (Saxod 1978). However, the epidermis of birds is completely free not only of Merkel cells and their nerve endings, but also of free nerve endings, which terminate in the dermis (Hemming et al. 1994). There is still controversy about the developmental origin of Merkel cells. According to one view, they originate from the neural crest and migrate into the mammalian epidermis during embryonic development. This opinion is supported by the observation of Merkel cells in the dermis of fetal and newborn mammalian skin (Breathnach and Robins 1970; Hashimoto 1972; Winkelmann 1977). Analternative view is that they arise from an ectodermal stem cell common to keratinocytes and Merkel cells (Munger 1965; English 1974; Moll
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