Dedicated Epithelial Recipient Cells Determine Pigmentation Patterns

Summary Mammals generate external coloration via dedicated pigment-producing cells but arrange pigment into patterns through mechanisms largely unknown. Here, using mice as models, we show that patterns ultimately emanate from dedicated pigment-receiving cells. These pigment recipients are epithelial cells that recruit melanocytes to their position in the skin and induce the transfer of melanin. We identify Foxn1 (a transcription factor) as an activator of this "pigment recipient phenotype" and Fgf2 (a growth factor and Foxn1 target) as a signal released by recipients. When Foxn1—and thus dedicated recipients—are redistributed in the skin, new patterns of pigmentation develop, suggesting a mechanism for the evolution of coloration. We conclude that recipients provide a cutaneous template or blueprint that instructs melanocytes where to place pigment. As Foxn1 and Fgf2 also modulate epithelial growth and differentiation, the Foxn1 pathway should serve as a nexus coordinating cell division, differentiation, and pigmentation.