Formation of epidermal and dermal Merkel cells during human fetal skin development

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 100 mm 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.