Immunohistochemical demonstration of nerve-Merkel cell complex in fetal human skin

Using Merkel cell specific antikeratin antibodies and neurofilament antibody the nerve-Merkel cell relationship was studied with a double staining method on frozen sections. Merkel cells were stained with monoclonal anti-cytokeratin CK-5 and CAM 5.2 which react against human cytokeratin polypeptide 45 kDa and 52.5 kDa, respectively. Peripheral nerves were stained with monoclonal murine antibody Neurofilament 70 and 200 kDa. Epidermal Merkel cells were recognized in 12-week fetuses in the plantar skin. In 15-week fetuses dermal Merkel cells were found. Most of the dermal Merkel cells initially lacked a close association with immunoreactive nerve fibers. In 16-week fetuses immunoreactive small nerves reached the epidermis and a few dermal Merkel cells became heavily entangled with the meshwork of nerve endings. Nerve-Merkel cell complex in the dermis was confirmed by electron microscopy. The appearance of epidermal Merkel cells preceded the attachment of immunoreactive nerve endings to the epidermis. In an analysis of 448 dermal Merkel cells the nerve-Merkel cell complex became more frequent as the age of fetus advanced. It was concluded that Merkel cells do not arrive at the epidermis with peripheral nerves. Rather, the peripheral nerves are attracted to the dermal Merkel cells which originated in the epidermis.