Mammalian Merkel Cells Are Neural Crest Derivatives

Abstract

We provide evidence for the neural crest origin of mammalian Merkel cells. Neural crest cells originate in the neural folds during early development of the vertebrate embryo. They delaminate from the dorsal aspect of the forming neural tube and emigrate to different locations, giving rise to a diverse array of structures in the adult organism. The dorsal neural tube, including neural crest cells, transiently express the protein, Wnt-1. This feature can be used to genetically mark neural crest cells and their derivatives. We have thus used the double transgenic Wntl -cre/R26R mouse to determine the ontogenetic origin of mammalian Merkel cells. Merkel cells in the hair follicle epithelium of the whisker pad, interfollicular Merkel cells in touch domes and Merkel cells in the rete ridge express the neural crest-specific transgene, s-galactosidase. Our data thus indicate that mammalian Merkel cells are derived from the neural crest, resolving a long-standing controversy. Moreover, they suggest that Merkel cell carcinomas are not epithelial tumors, but belong to the neurocristopathies.