Skin as Living Coloring Book
Melanin (insoluble pigment that gives color to skin & hair) is produced by Melanocytes (cell in the basal layer of skin) and then distributed to other cells. But not every cell in layers of skins gets pigmented.
Researchers at the Massachusetts General Hospital (MGH) Cutaneous Biology Research Center (CBRC) have answered the question about delivery of melanin to appropriate locations.
“Pigment recipient cells essentially tell Melanocytes where to deposit melanin, and the pattern of those recipients determines pigment patterns. Recipient cells act like the outlines in a child’s coloring book; as recipient cells develop, they form a ‘picture’ that is initially colorless but is then ‘colored in’ by the Melanocytes.” said Janice Brissette (lead researcher).
Humans’ melanin is deposited in both the skin and hair whereas in mammals like mice it is deposited primarily in the coat, leaving the skin beneath the coat un-pigmented. Melanocytes deposit melanin through cellular extensions called dendrites that extend to other cells in the epidermis (the outer layer of skin) or the hair follicles. But the mechanism that determines whether melanin is delivered to a particular cell is unknown.
The MGH-CBRC research team supposed that a mouse gene known as Foxn1 might have some involvement. Lack of Foxn1 is responsible for ‘nude mice,’ which possess hair that are brittle and this leads to complete hairlessness and other skin diseases. A similar disorder exists in humans with inactivation of the related gene.
The researchers developed a strain of transgenic mice in which Foxn1 was misexpressed in cells that do not synthesize melanin because of which normally colorless areas became pigmented. When they examined the skin of the transgenic mice it appeared that Melanocytes were contacting and delivering melanin to the cells that had Foxn1 abnormally activated. The corresponding tissues of normal mice had no pigment.
Examination of human skin samples revealed the human version of Foxn1 which was also expressed in cells known to be pigment recipient cells. Further experimentation exposed that the Foxn1 signals Melanocytes through a protein called Fgf2 whose levels rise with the rise in Foxn1 expression.
“Foxn1 makes epithelial cells into pigment recipients, which attract Melanocytes and stimulate pigment transfer, engineering their own pigmentation,” says Brissette. She and her team still signals that the Foxn1/Fgf2 pathway probably has additional functions in the skin and there may be other pathways responsible for the targeting of pigment.
“We know that Foxn1 and Fgf2 act in concert with other factors and function within a larger network of genes. Our next step will be to identify other genes that can confer the pigment recipient phenotype or control the targeting of pigment,” added Brissette. Her research explains disorders such as Vitiligo, age spots, the graying of hair and even the deadly melanocyte-based skin cancer melanoma.