Merkel Cells in Mouse Skin: Intermediate Filament Pattern, Localization, and Hair Cycle-Dependent Density

Abstract

The distribution and antigen expression of Merkel cells in mouse skin is as yet ill defined. Since the mouse offers an excellent model for studying the origin and functions of Merkel cells, the Merkel cell distribution as well as the expression of intermediate filament proteins and neuronal markers was characterized in C57 BL/6 mouse skin by immunohistochemistry and electron microscopy. Merkel cells in whisker pads, back, and foot pad skin as identified by staining for neuron-specific enolase-an established neuroendocrine marker--expressed cytokeratins (CK) 8,18, and 20 (i.e., simple-epithelial CKs), but not CKs 4 and 13. Sequential double staining for neuron-specific enolase and CK 20 showed consistent co-expression in Merkel cells, establishing CK 20 as a specific immunocytochemical marker for mouse Merkel cells. The Merkel cells also were immunoreactive for synaptophysin but not for neurofilament proteins, peripherin, S-100 protein, and neural cell adhesion molecule. Using CK 8, 18, and 20 as markers, we detected many Merkel cells in the outer roots sheath of vibrissae hair follicles and in foot pad skin. However, only few Merkel cells were found in back skin. These were restricted to small clusters, localized basally within the Haarscheiben epidermis of tylotrich hair follicles, and formed close contacts to prominent nerve fiber terminals as shown by electron microscopy. In striking contrast to human skin, Merkel cells were never found in the epithelium of pelage hair follicles. Even more strikingly, the density of Haarscheiben-associated Merkel cells changed substantially during the highly synchronized, depilation-induced C 57 BL/6 hair cycle, with a minimum in back skin with all hair follicles in telogen or catagen, and a maximum in back skin with all hair follicles in anagen IV-VI. These observations on the Merkel cell hair cycle-dependent distribution in murine skin point to important differences in Merkel cell functions between humans and mice, and raise intriguing questions as to the role of Merkel cells in hair biology.