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Skin as a living coloring book
Specialized recipient cells
determine where pigment is deposited in epidermis and hair
BOSTON - September 6, 2007 - The pigment melanin, which is
responsible for skin and hair color in mammals, is produced in specialized
cells called melanocytes and then distributed to other cells. But
not every cell in the complex layers of skin becomes pigmented.
The question of how melanin is delivered to appropriate locations
may have been answered by a study from researchers at the Massachusetts
General Hospital (MGH) Cutaneous
Biology Research Center (CBRC).
"Pigment recipient cells essentially tell melanocytes where
to deposit melanin, and the pattern of those recipients determines
pigment patterns," says Janice Brissette, PhD, who led the
study. "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."
The report appears in the Sept. 7 issue of Cell.
In humans, melanin is deposited in both the skin and the hair; but
in some other mammals such as mice, melanin is primarily deposited
in the coat, leaving the skin beneath the coat unpigmented. Melanocytes
deposit melanin via cellular extensions called dendrites that reach
out to other cells in the epidermis (the outer layer of skin) or
the hair follicles. But the mechanism determining whether melanin
is delivered to a particular cell has been unknown.
The MGH-CBRC researchers theorized that a mouse gene known as Foxn1
might play a role. Lack of Foxn1 is responsible for so-called 'nude
mice,' which have hair that is so brittle it breaks off, resulting
in virtually total hairlessnes, and other defects of the skin. A
similar phenomenon exists in humans with inactivation of the corresponding
gene.
When the researchers developed a strain of transgenic mice in which
Foxn1 is misexpressed in cells that do not usually contain melanin,
they found those normally colorless areas became pigmented. Examining
the skin of the transgenic mice revealed that melanocytes were contacting
and delivering melanin to the cells in which Foxn1 was abnormally
activated. No pigment was observed in the corresponding tissues
of normal mice. Examination of human skin samples showed that the
human version of Foxn1 was also expressed in cells known to be pigment
recipients. Further experiments revealed that Foxn1 signals melanocytes
through a protein called Fgf2, levels of which rise as Foxn1 espression
increases.
"Foxn1 makes epithelial cells into pigment recipients, which
attract melanocytes and stimulate pigment transfer, engineering
their own pigmentation," says Brissette, an associate professor
of Dermatology at Harvard Medical School. She and her colleagues
note that the Foxn1/Fgf2 pathway probably has additional functions
in the skin and that it is probably not the only pathway 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," Brissette adds.
Her research may eventually be relevant to disorders such as vitiligo
- in which pigment disappears from patches of skin - age spots,
the greying of hair and even the deadly melanocyte-based skin cancer
melanoma.
The co-first authors of the Cell report are Lorin Weiner,
PhD, and Rong Han, PhD, both of the MGH-CBRC. Additional co-authors
are Jian Li, PhD, Kiyotaka Hasegawa, MS, and David Lee, MGH-CBRC;
Bianca Scicchitano, PhD, now at La Sapienza/University of Rome;
and Maddalena Grossi, PhD, University of Lausanne, Switzerland.
The study was supported by the National Institutes of Health and
by the CBRC through the support of Shiseido Co. Ltd.
Massachusetts General Hospital, established in 1811, is the original
and largest teaching hospital of Harvard Medical School. The MGH
conducts the largest hospital-based research program in the United
States, with an annual research budget of nearly $500 million and
major research centers in AIDS, cardiovascular research, cancer,
computational and integrative biology, cutaneous biology, human
genetics, medical imaging, neurodegenerative disorders, regenerative
medicine, systems biology, transplantation biology and photomedicine.
MGH and Brigham and Women's Hospital are founding members of Partners
HealthCare HealthCare System, a Boston-based integrated health care
delivery system.
Media Contacts: Emily
Parker, MGH Public Affairs
Sue McGreevey,
MGH Public Affairs
Physician Referral Service: 1-800-388-4644
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