Original Article

Journal of Investigative Dermatology (1986) 87, 779–787; doi:10.1111/1523-1747.ep12458993

Formation of Epidermal and Dermal Merkel Cells During Human Fetal Skin Development

Ingrid Moll1, Roland Moll2 and Werner W Franke3

  1. 1Department of Dermatology, Mannheim Medical School, University of Heidelberg, Mannheim, F.R.G.
  2. 2Department of Pathology, University of Mainz, Mainz, F.R.G.
  3. 3Division of Membrane Biology and Biochemistry, Institute of Cell and Tumor Biology, German Research Center, Heidelberg, F.R.G.

Received 11 April 1986; Accepted 17 June 1986.

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Abstract

The origin of Merkel cells is still a matter of debate, specifically the question of whether they are derived from epithelial cells of the epidermis or from immigrated neural crest cells. As an argument for the latter hypothesis the occurrence of dermal, nerve-associated Merkel cells in human fetal skin has often been mentioned. Therefore, we analyzed the distribution of Merkel cells in epidermis and dermis of plantar skin of human embryos and fetuses, ranging in gestational age between 7 and 17 weeks. Merkel cells were identified by immunocytochemistry on frozen sections using antibodies against simple epithelium-type cytokeratins and by electron microscopy. In the 17-week-old fetus, 17% of the total cutaneous (epidermal and dermal) Merkel cells were located in the upper dermal compartment, whereas in the 14-week-old fetus only 3.9% of the Merkel cells were dermal, including some cells that seemed to be in the process of traversing the dermal-epidermal junction. Thirteen-week-old fetuses showed even fewer dermal Merkel cells. Twelve-week-old fetuses exhibited 660 epidermal Merkel cells per 100mm total section length, but none in the upper or deep dermis. In 7- to 9-week embryos, no Merkel cells were recognized. However, at this stage, but not in later stages, the basal cells of the plantar epidermis expressed certain simple epithelium-type cytokeratin polypeptides. These results speak against an invasion of Merkel cells or putative neural crest-derived precursor cells into the epidermis via a dermal passage. They suggest that in plantar skin Merkel cells arise, between weeks 8-12, from precursor stages of epithelial cells of the early fetal epidermis which still express simple epithelium-type cytokeratins. The results further suggest that in subsequent stages of skin development some epidermal Merkel cells detach from the epithelium and migrate into the upper dermis where some of them may associate with small nerves.

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References

  1. Breathnach, AS: The mammalian and avian Merkel cell. The Skin of Vertebrates 1979 Edited by RIC Spearman, PA Riley. Dorchester, Dorset, Henry Ling, Dorset Press, Linnean Society Series no. 9, pp 283–291,
  2. Hartschuh, W, Weihe, E, Reinecke, M: The Merkel cell. Biology of the Integument, vol. 2, Vertebrates 1986 Edited by J Bereiter-Hahn, AG Maltoltsy, KS Richards. Berlin/Heidelberg/New York, Springer-Verlag, pp 605–617,
  3. Munger, B: The intra-epidermal innervation of the snout skin of the oppossum. A light and electron microscope study with observation on the nature of Merkel's Tastzelle. J Cell Biol 1965 26: 79–97,  | Article | PubMed | ChemPort |
  4. Kurosumi, K, Kurosumi, U, Inoue, K: Morphological and morphometric studies with the electron microscope on the Merkel cells and associated nerve terminals of normal and denervated skin. Arch Histol Jpn 1979 42: 243–261,  | PubMed | ChemPort |
  5. Smith, KR: The ultrastructure of the human Haarscheibe and Merkel cell. J Invest Dermatol 1970 54: 150–159,  | PubMed |
  6. English, KB: Morphogenesis of Haarscheiben in rats. J Invest Dermatol 1977 69: 58–67,  | Article | PubMed | ChemPort |
  7. Moll, R, Moll, I, Franke, WW: Identification of Merkel cells in human skin by specific cytokeratin antibodies: changes of cell density and distribution in fetal and adult plantar epidermis. Differentiation 1984 28: 136–154,  | PubMed | ISI | ChemPort |
  8. Saurat, JH, Didierjean, L: The epidermal Merkel cell is an epithelial cell. Dermatologica 1984 169: 117–120,  | PubMed | ChemPort |
  9. Saurat, JH, Didierjean, L, Skalli, O, Siegenthaler, G, Gabbiani, G: The intermediate filament proteins of normal epidermal rabbit Merkel cells arc cytokeratins. J Invest Dermatol 1984 83: 431–435,  | Article | PubMed | ChemPort |
  10. Gould, VE, Moll, R, Moll, I, Lee, I, Franke, WW: Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest 1985 52: 334–353,  | PubMed | ChemPort |
  11. Lane, EB, Bártek, J, Purkis, PE, Leigh, IM: Keratin antigens in differentiating skin, Intermediate Filaments. Ann NY Acad Sci 1985 455: 241–258,  | PubMed | ChemPort |
  12. Ortonne, JP, Darmon, M: Merkel cells express desmosomal proteins and cytokeratins. Acta Derm Venerol (Stockh) 1985 65: 161–164,  | ChemPort |
  13. Tweedle, CD: Ultrastructure of Merkel development in aneurogenic and control amphibian larvae (Ambystoma). Neuroscience 1978 3: 481–486,  | Article | PubMed | ChemPort |
  14. Tachibana, T, Ishizeki, K: Merkel cell development in the wound healing in the labial mucosa of adult rabbits. Arch Histol Jpn 1981 44: 151–165,  | PubMed | ChemPort |
  15. Hashimoto, K: The ultrastructure of human embryos. X. Merkel tactile cells in the finger and nail. J Anat 1972 111: 99–120,  | PubMed | ChemPort |
  16. Winkelmann, RK: The Merkel cell system and a comparison between it and the neurosecretory or APUD cell system. J Invest Dermatol 1977 69: 41–46,  | Article | PubMed | ChemPort |
  17. Winkelmann, RK, Breathnach, AS: The Merkel cell. J Invest Dermatol 1973 60: 2–15,  | Article | PubMed | ChemPort |
  18. Breathnach, AS: Embryology of human skin: a review of ultrastructural studies. J Invest Dermatol 1971 57: 133–143,  | Article | PubMed | ChemPort |
  19. Breathnach, AS: Ultrastructure of embryonic skin. Curr Probl Dermatol 1981 9: 1–28,  | PubMed | ChemPort |
  20. Streeter, GL: Weight, sitting height, head size, foot length, and menstrual age of the human embryo. Contributions to Embryology 1920 11: 143–170,
  21. Franke, WW, Schmid, E, Freudenstein, C, Appelhans, B, Osborn, M, Weber, K, Keenan, TW: Intermediate-sized filaments of the prekeratin type in myoepithelial cells. J Cell Biol 1980 84: 633–654,  | Article | PubMed | ISI | ChemPort |
  22. Debus, E, Weber, K, Osborn, M: Monoclonal cytokeratin antibodies that distinguish simple from stratified squamous epithelial: characterization on human tissues. EMBO J 1982 1: 1641–1647,  | PubMed | ISI | ChemPort |
  23. Moll, R, Franke, WW, Schiller, DL, Geiger, B, Krepler, R: The catalog of human cytokeratin polypeptides: patterns of expression of specific cytokeratins in normal epithelial, tumors and cultured cell. Cell 1982 31: 11–24,  | Article | PubMed | ISI | ChemPort |
  24. Ramackers, F, Hysmans, A, Moesker, O, Kant, A, Jap, P, Herman, C, Vooijs, P: Monoclonal antibody to keratin filaments specific for glandular epithelia and their tumors. Lab Invest 1983 49: 353–361,  | PubMed | ChemPort |
  25. Moll, R, Franke, WW: Cytoskeletal differences between human neuroendocrine tumors: a cytoskeletal protein of molecular weight 46,000 distinguishes cutaneous from pulmonary neuroendocrine neoplasms. Differentiation 1985 30: 165–175,  | PubMed | ChemPort |
  26. Huszar, M, Gigi-Leitner, O, Moll, R, Franke, WW, Geiger, B: Polypeptide-specific monoclonal cytokeratin antibodies in the differential diagnosis of squamous carcinomas and adenocarcinomas. Differentiation in press
  27. Nagle, BR, Moll, R, Weidauer, H, Nemetschek, H, Franke, WW: Different patterns of cytokeratin expression in the normal epithelia of the upper respiratory tract. Differentiation 1985 30: 130–140,  | PubMed | ChemPort |
  28. Miettinen, M, Clark, R, Lehto, V-P, Virtanen, I, Damjanov, I: Intermediate filament proteins in parathyroid glands and parathyroid adenomas. Arch Pathol Lab Med 1985 109: 986–989,  | PubMed | ChemPort |
  29. Karsten, U, Papsdorf, G, Roloff, G, Stolley, P, Abel, H, Walther, I, Weiss, H: Monoclonal anti-cytokeratin antibody from a hybridoma clone generated by electrofusion. Eur J Cancer Clin Oncol 1985 21: 733–740,  | Article | PubMed | ChemPort |
  30. Shaw, G, Weber, K: Differential expression of neurofilament triplet protein in brain development. Nature 1982 298: 227–229,  | Article |
  31. Shaw, G, Weber, K: The distribution of the neurofilament triplet proteins within individual neurones. Exp Cell Res 1981 136: 119–125,  | Article | PubMed | ChemPort |
  32. Debus, E, Weber, K, Osborn, M: Monoclonal antibodies specific for glial fibrillary acidic (GFA) protein and for each of the neurofilament triplet polypeptides. Differentiation 1983 25: 193–203,  | PubMed | ISI | ChemPort |
  33. Van Muijen, GNP, Ruiter, DJ, Van Leeuwen, C: Cytokeratin and neurofilaments in lung carcinomas. Am J Pathol 1984 116: 363–369,  | PubMed | ChemPort |
  34. Franke, WW, Lüder, MR, Kartenbeck, J, Zerban, H, Keenan, TW: Involvement of vesicle coat material in casein secretion and surface regeneration. J Cell Biol 1976 69: 173–195,  | Article | PubMed | ISI | ChemPort |
  35. Breathnach, AS, Robins, J: Ultrastructural observations on Merkel cells in human fetal skin. J Anat 1970 106: 411–419,  | PubMed | ChemPort |
  36. Saurat, HJ, Didierjean, L, Dahl, D: Normal rabbit Merkel cells (MC) do not express the intermediate filament protein of glial or neuronal cells (abstr). J Invest Dermatol 1984 82: 424,
  37. Saurat, JH, Merot, Y, Didierjean, L, Dahl, D: Normal rabbit Merkel cells do not express neurofilament proteins. J Invest Dermatol 1984 82: 641–642,  | Article | PubMed | ChemPort |
  38. Miettinen, M, Lehto, V-P, Asko-Seljavaara, S, Pitkänen, J, Dahl, D: Neuroendocrine carcinoma of the skin (Merkel cell carcinoma): ultrastructural and immunohistochemical demonstration of neurofilaments. Ultrastruct Pathol 1983 4: 219–225,  | PubMed | ChemPort |
  39. Hoefler, H, Kerl, H, Rauch, H-J, Denk, H: New immunocytochemical observations with diagnostic significance in cutaneous neuroendocrine carcinoma. Am J Dermatopathol 1984 6: 525–530,  | PubMed | ChemPort |
  40. Tachibana, T, Nawa, T: Merkel cell differentiation in the labial mucous epithelium of the rabbit. J Anat 1979 131: 145–155,
  41. Saxod, R: Development of Merkel corpuscles in the chicken beak. The problem of their origin and identity. Biol Cell 1980 37: 61–66,
  42. Moll, R, Moll, I, Wiest, W: Changes in the pattern of cytokeratin polypeptides in epidermis and hair follicles during skin development in human fetuses. Differentiation 1982 23: 170–178,  | PubMed | ISI | ChemPort |
  43. Baden, HP, Lee, LD: Fibrous protein of human epidermis. J Invest Dermatol 1978 71: 148–151,  | PubMed | ChemPort |
  44. Fuchs, E, Green, H: Changes in keratin gene expression during terminal differentiation of the keratinocyte. Cell 1980 19: 1033–1042,  | Article | PubMed | ISI | ChemPort |
  45. Woodcock-Mitchell, J, Eichner, R, Nelson, WG, Sun, T-T: Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol 1982 95: 580–588,  | Article | PubMed | ChemPort |
  46. Dale, BA, Holbrook, KA, Kimball, JR, Hoff, M, Sun, T-T: Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol 1985 101: 1257–1269,  | Article | PubMed | ISI | ChemPort |
  47. Regauer, S, Franke, WW, Virtanen, J: Intermediate filaments cytoskeleton of aminion epithelial cells: expression of epidermal cytokeratins in cells of a simple epithelium. J Cell Biol 1985 100: 997–1009,  | Article | PubMed | ISI | ChemPort |
  48. Anderson, AE, Nafstad, PHJ: An electron microscopic investigation of the sensory organs in the hard palate region of the hen (Gallus domesticus). Z Zellforsch Mikroskop Anat 1968 91: 391–401,
  49. Saxod, R: Etude au microscope électronique de l'histogenèse du corpuscule sensoriel cutané de Grandry chez le canard. J Ultrastruct Res 1970 32: 477–496,  | Article | PubMed | ChemPort |
  50. Garant, PR, Feldman, J, Cho, MI, Cullen, MR: Infrastructure in the hard palate of the squirrel monkey (Saimiri sciureus). Am J Anat 1980 157: 155–167,  | Article | PubMed | ChemPort |
  51. Le Douarin, N: The Neural Crest. Developmental and Cell Biology Series 1982 Edited by PW Barlow, PB Green, CC Wylie. Cambridge/London/New York/New Rockalle/Melbourne/Sydney, Cambridge Univ Press, pp 91–107,
  52. Pearse, AGE, Polak, J: Immunocytochemical localization of substance P in mammalian intestine. Histochemistry 1975 41: 373–375,  | Article | PubMed | ISI | ChemPort |
  53. Tachibana, T, Ishizeki, K, Sakakura, Y, Nawa, T: Ultrastructural evidence for a possible secretory function of Merkel cells in the barbels of a teleost fish, Cyprinus carpio. Cell Tissue Res 1984 235: 695–698,  | PubMed | ChemPort |
  54. Kemmner, W, Schaller, HC: Actions of head activator and head inhibitor during regeneration in hydra. Differentiation 1984 26: 91–96,
  55. Diamond, I: The regulation of nerve sprouting by extrinsic influences. The Neurosciences: Fourth Study Program 1979 Edited by FO Schwitt, FC Worden. Boston, Massachusetts Institute of Technology Press, pp 937–955,
  56. Gould, VE, Linnoila, RI, Memoli, VA, Warren, WH: Neuroendocrine components of the bronchopulmonary tract: hyperplasias, dysplasias, and neoplasms. Lab Invest 1983 49: 519–537,  | PubMed | ISI | ChemPort |
  57. Cuttitta, F, Carney, DN, Mulshine, J, Moody, TW, Fedorko, J, Fischler, A, Minna, JD: Bombesin-like peptides can function as autocrine growth factors in human small cell lung cancer. Nature 1985 316: 823–826,  | Article | PubMed | ISI | ChemPort |

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