A genetic pathway

Sep 7, 2007 09:27 GMT  ·  By

What makes people black or white (and not only people)? It's the pigment melanin (or its scarcity), which blackens the skin and hair in mammals. The pigment is synthesized in specialized cells, melanocytes and then delivered to other cells. But not all the skin cells are loaded with melanin. A team at the Massachusetts General Hospital (MGH) Cutaneous Biology Research Center (CBRC) has found how melanin is transported to the right places.

"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 lead researcher Dr. Janice Brissette, an associate professor of Dermatology at Harvard Medical School.

In humans, both the skin and the hair contain melanin; but in some mammals, like mice, melanin is primarily stored in the coat, while the skin beneath the hair is largely unpigmented. Melanocytes transport melanin through cellular extensions named dendrites that go to other epidermis (outer skin) cells or the hair follicles.

But how the melanin delivered the pigment to specific cells was not known. The research team supposed that a mouse gene called Foxn1 could be involved. Its lack causes the 'nude mice,' which possess a hair so brittle that it breaks off, leading to complete hairlessness and other skin disorders. A similar disease is induced in humans by the shut off of the similar gene.

The team engineered a breed of mice in which Foxn1 was shut off in cells that do not synthesize melanin and observed that normally colorless areas turned pigmented. It appeared that melanocytes were sending melanin to the cells with a deactivated Foxn1.

The corresponding tissues of mice with a shut off Foxn1 have no melanin. Human skin samples revealed that Foxn1 was active in pigment recipient cells. The experiments have revealed that Foxn1 signals melanocytes to deliver melanin through a protein called Fgf2, whose levels increase as Foxn1 expression rises.

"Foxn1 makes epithelial cells into pigment recipients, which attract melanocytes and stimulate pigment transfer, engineering their own pigmentation," says Brissette. Still, her team signals that there may be also other pathways besides the Foxn1/Fgf2 controlling the melanin amounts in the cells.

"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.

This kind of researchers explains issues like vitiligo (when pigment is not present in patches of skin, giving a mottled look) (remember how Michael Jackson justified his bleaching operations?), age spots, the hair graying, the mottled patterns on animals and even the deadly melanocyte-based skin cancer melanoma.