To survive in this world, you must develop a thick skin - literally. The thick, outer layer of skin - the epidermis - is what separates us from the outside world, keeping in moisture and functioning as a defense against the environment. The skin is not fully developed until shortly before birth. Therefore, prematurely born infants are defective in the skin barrier and at risk for medical complications such as dehydration, difficulties maintaining body temperature, infection and skin breakdown.

New findings by NIAMS-supported researchers, however, could potentially lead to ways to speed skin maturation in tiny babies at risk for these problems. While such therapies are still years away, they are a step closer, thanks to a better understanding of how normal skin develops and more specifically how embryonic cells develop into epidermal cells.

The epidermis, the outer 10 percent of the skin, is composed of an inner layer (known as the basal layer) of dividing cells that give rise to approximately 10 differentiated layers, the outermost of which is our body's surface. Unlike embryonic stem cells - precursor cells that can become virtually any cell of the body - epidermal stem cells can only differentiate into those 10 layers of skin, says Elaine Fuchs, Ph.D., head of the Laboratory of Mammalian Cell Biology and Development at Rockefeller University, who led the research.

In this study, the researchers focused on the enzyme Ezh2, because past research had shown the enzyme blocked access to skin-differentiation genes in embryonic stem cells, yet its role in skin stem cells had never been explored in a living animal.

Working with other researchers at Rockefeller University, Fuchs's team bred mice with and without Ezh2. They found that mice without the enzyme were born with thicker skin than their normal counterparts. Without Ezh2 to block access to the skin differentiation genes, the skin stem cells differentiate and form skin much earlier than in normal mice.

"In our mice we have acceleration of skin differentiation and skin development," says Elena Ezhkova, Ph.D., a postdoctoral student in Fuch's lab and co-author of the study. "Skin development occurred properly, it just occurred much earlier."

This study provides insights into possible drug development targets for accelerating the maturation of the skin in prematurely-born infants. But for now, the researchers' goal is to continue to gain a basic understanding of skin development, says Ezhkova.

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Ezhkova E, Pasolli HA, Parker JS, Stokes N, Su I-hsin, Hannon G, Tarakhovsky A, Fuchs E. Ezh2 Orchestrates Gene Expression for the Stepwise Differentiation of Tissue-Specific Stem Cells. Cell. 2009 March; 136 (6)1122-1135.

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