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Spotlight on Research 2008

June 2008 (historical)

Cell-signaling System Helps Explain How Skin Develops Into Different Types

Your skin protects you from infections, regulates your body temperature, eliminates waste products, and allows you to feel the world around you. It's no surprise, then, that not all skin does exactly the same job. Scientists have known for some time that skin cells in different parts of the body can adapt their function to their specific location. The process governing this adaptation has not been well understood, but researchers supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) cleared up some of the mystery recently with findings about a cell-signaling system that influences skin tissue development. Their findings could someday contribute to new ways of treating skin diseases.

Because all skin cells originate from the same pool of less-specialized progenitor cells, scientists have suspected that skin cells must be receiving signals that instruct them to develop differently depending on their location in the body. What the NIAMS-funded researchers have discovered are some of the components and steps of that signal system and how it operates in skin.

The pattern of distinct functional characteristics that cells have in different parts of the body is known by skin researchers as “positional identity.” Positional identity allows cells to pinpoint where they are so they know how to behave. According to Howard Y. Chang, M.D., Ph.D., an assistant professor of dermatology at Stanford University School of Medicine and one of the leaders of the research team, “This system is kind of like a global positioning device in the skin because it really tells cells whether they are on the top half of the body or the bottom half, whether they're on the outside – the skin surface – or inside lining organs, and whether they are close to the center of the body or away from it, such as on the hands and feet.” Chang said it is like longitude and latitude on a map, except that in this case there are three sets of coordinates.

Work published by the researchers last summer in the journal Cell showed that positional information is preserved in the skin cell's chromatin, a complex of deoxyribonucleic acid (DNA) and protein in the cell's nucleus where the genes reside. They also showed that there is a different stretch of DNA for each of the three positional axes, meaning that there is actually a physical manifestation of the positional memory.

The group's latest research, published February in Genes & Development , explained how this kind of memory might work. They discovered that HOX genes, master-switch genes that encode proteins that turn genes on and off, become active based on a cell's location in the body. And activated HOX genes then turn on other genes that instruct surrounding cells in the skin how to behave. Although researchers already knew that HOX genes play a role in embryonic development, their possible role in adult cells was unknown until now .

The scientists said that a better understanding of the skin-cell positioning system may provide opportunities for research on the treatment of skin diseases that affect only particular parts of the body, such as eczema that affects just the hands, elbows and knees. Furthermore, the possibility that HOX genes play a role in adult skin cells by specifying and maintaining functional properties according to body region could have important implications for tissue engineering, wound healing and cell-based therapies.

The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. For more information about NIAMS, call the information clearinghouse at 301-495-4484 or 877-22-NIAMS (free call) or visit the NIAMS Web site at


Rinn JL, et al . A dermal HOX transcriptional program regulates site-specific epidermal fate. Genes Dev 2008;22:303-07.

Rinn JL, et al . Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Cell 2007;129:1-12.