Since melanocytes are the givers of melanin, they've been the focus of studies on coloration. “But we are now showing that epithelial cells tell the melanocytes what to do,” says Brissette. “It's analogous to a child's coloring book. Pigment recipients collectively form the outline of the picture, where the pigments should be placed. And the melanocytes color in the picture.”
Brissette's group is interested in a transcription factor called Foxn1 and its role in the skin. For functional studies, they created mice whose skin precursor cells made extra Foxn1. The mice developed dark skin that had extra melanocytes. As the mice matured, the cells making Foxn1 became sparser. Melanocytes persisted mainly near the remaining Foxn1-expressing cells, suggesting that those cells might help melanocytes survive or proliferate.
One survival factor that melanocytes don't make themselves but do need in culture is Fgf2. The authors found that Foxn1 activated Fgf2 expression, resulting in its secretion from epithelial cells. Blocking Fgf2 activity killed off the extra melanocytes in the transgenic mice.
Humans, who have darker skin than do mice, expressed Foxn1 more widely in epithelial cells. But whether Foxn1 defects cause human pigmentation diseases is not yet known.