Abstract
The fetal development of Merkel cells-neuroendocrine cells of the skin—has been a matter of debate for a long time. Recent results have helped to confirm their intraepidermal development in humans. Simple epithelial cytokeratins (CK) nos. 8, 18, 19 and 20 are well established markers at the light microscopic level. These cells could be detected from fetal week 8 within the epidermis with an enormous increase during the following weeks. This gives rise to the question as to whether Merkel cells are undergoing mitoses or whether they are derived from basal keratinocytes. We studied fetal and adult skin using antibodies to simple epithelial CK and to Ki67, a human nuclear cell proliferation-associated antigen in an attempt to answer these questions. In human adult and fetal skin of various stages we could not detect any Merkel cells undergoing cell division. These results suggest that Merkel cells are postmitotic cells to be renewed from undifferentiated keratinocytes with stem cell characteristics.
Similar content being viewed by others
References
Burgess PR, English KB, Horch KW, Stensaas LJ (1974) Patterning in the regeneration of type I cutaneous receptor. J Physiol 236:7–82
Cattoretti G, Becker MHG, Key G, Duchrow M, Schlüter C, Galle J, Gerdes J (1992) Monoclonal antibodies against recombinant parts of the Ki 67-antigen (MIB 1 and MIB 3) detect proliferating cells in microwave-processed formalin-fixed paraffin sections. J Pathol 168:357–363
Compton CC, Regauer S, Seiler GT, Landry DB (1990) Human Merkel cell regeneration in skin derived from cultured keratinocyte grafts. Lab Invest 62:233–241
English KB (1977) Morphogenesis of Haarscheiben in rats. J Invest Dermatol 69:58–67
Franke WW, Moll R (1987) Cytoskeletal components of lymphoid organs. I. Synthesis of cytokeratins 8 and 18 and desmin in subpopulations of extrafollicular reticulum cells of human lymph nodes, tonsils, and spleen. Differentiation 36:145–163
Franke WW, Schmid E, Freudenstein C, Appelhans B, Osborn M, Weber K, Keenan TW (1980) Intermediate-sized filaments of the prekeratin type in myoepithelial cells. J Cell Biol 84:633–654
Gerdes J, Lemke H, Boisch H et al. (1984) Cell cycle analysis of a cell proliferation associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715
Gould VE, Moll R, Moll I, Lee J, Franke WW (1985) Neuroendocrine (Merkel) cells of the skin: hyperplasias dysplasias, and neoplasms. Lab Invest 52:334–353
Lacour JP, Dubois D, Pisani D, Ortonne JP (1991) Anatomical mapping of Merkel cells in normal human adult epidermis. Br J Dermatol 125:535–542
Mercer BM, Sklar S, Shariatmadar A, Gillieson MS, D’Alton ME (1987) Fetal foot length as a predictor of gestational age. Am J Obstet Gynecol 156:350–355
Mérot Y, Mooy A (1989). Merkel cell hyperplasia in hypertophic varieties of actinic keratoses. Dermatologica 178:189–193
Mérot Y, Chavaz P, Carraux P, Polla L, Saurat JH (1986) Merkel cells do divide in the epidermis (abstr). J Invest Dermatol 87:155
Mérot Y, Carraux P, Saurat JH (1987) Merkel cell mitoses in vibrissae: An ultrastuctural study. J Anat 153:241–244
Moll I, Moll R (1992) Early development of human Merkel cells. Exp Dermatol 1:180–184
Moll I, Moll R, Franke WW (1986). Formation of epidermal and dermal Merkel cells during human fetal skin development. J Invest Dermatol 87:779–787
Moll I, Lane AT, Franke WW, Moll R (1990). Intraepidermal formation of Merkel cells in xenografts of human fetal skin. J Invest Dermatol 94:359–364
Moll I, Bladt U, Jung EG (1990) Presence of Merkel cells in sun-exposed and not sun-exposed skin: a quantitative study. Arch Dermatol Res 282:213–216
Moll I, Troyanovsky SM, Moll R (1993) Special program of differentiation expressed in keratinocytes of human Haarscheiben: An analysis of individual cytokeratin polypeptides. J Invest Dermatol 100:69–76
Moll I, Kuhn C, Moll R (1995) Cytokeratin 20 is a general marker of cutaneous Merkel cells while certain neuronal proteins are absent. J Invest Dermatol 104:910–915
Moll R, Franke WW, Schiller DL, Geiger B, Krepler R (1982) The catalog of human cytokeratins: patterns of expression in normal epithelia, tumours and cultured cells. Cell 31:11–24
Moll R, Moll I, Franke WW (1984) Identification of Merkel cells in human skin by specific cytokeratin antibodies: changes of cell density and distribution in fetal and adult plantar epidermis. Differentiation 28:136–154
Moll R, Schiller DL, Franke WW (1990) Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. J Cell Biol 111:567–580
Morohunfola K, Jones TE, Munger BL (1992) The differentiation of the skin and its appendages. I. Normal development of papillary ridges. Anat Rec 232:587–598
Narisawa Y, Hashimoto K, Bayless T, Nihei Y, Ishihara M, Lawrence D, Eto H, Hori K (1992) Cytokeratin polypeptide profile of Merkel cells in human fetal and adult skin: difference of expression of cytokeratins in epidermal and dermal Merkel cells. J Invest Dermatol 98:171–180
Streeter GL (1920) Weight, sitting height, head size foot length, and menstrual age of the human embryo. Contrib Embryol 11:143–170
Tachibana T, Nawa T (1979) Merkel cell differentiation in the labial mucous epithelium of the rabbit. J Anat 131:145–155
Vaigot P, Pisani A, Darmon YM, Ortonne JP (1987) The majority of epidermal Merkel cells are non-proliferative: a quantitative immunofluorescence analysis. Acta Derm Venereol (Stockh) 67:515–541
Watt FM, Jones PH (1993) Expression and function of the keratinocytes integrins. Development (Suppl) 119:185–192
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Moll, I., Zieger, W. & Schmelz, M. Proliferative merkel cells were not detected in human skin. Arch Dermatol Res 288, 184–187 (1996). https://doi.org/10.1007/BF02505222
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02505222