Scientists supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), as well as several other NIH components and the Howard Hughes Medical Institute, reported findings in the journals Developmental Biology and Science that should help resolve two longstanding controversies about Merkel cells: where they come from and their role in sensory perception.
Merkel cells, named after the German scientist who first described them in 1875, reside in the skin near nerve endings. Almost since that discovery, scientists have debated whether Merkel cells derive from embryonic skin cells or nerve cells. They also have disagreed about the role that Merkel cells play in the detection of touch.
Now, in a study described in Developmental Biology, a research team from Baylor College of Medicine, in Houston, and from Case Western Reserve University in Cleveland, determined that Merkel cells in mice come from precursor embryonic skin tissue, not from precursor nerve tissue, as some scientists had previously concluded. Key to this work was using an advanced genetic technique, called conditional gene knockout, that allowed the team to create mice that lack an essential gene for Merkel cell development, the Atoh1 gene, in selected parts of the body. When the team eliminated the gene from embryonic nerve tissue in one strain of mice, those mice still developed Merkel cells. Therefore, nerve tissue could not be the origin. But, when the researchers eliminated Atoh1from embryonic skin tissue, they hit the mark: these mice did not produce Merkel cells.
In a concurrent line of research reported in Science, the Baylor-Case Western team used similar mouse breeding techniques to study the role that Merkel cells play in sensation. Scientists have long been divided about whether or not Merkel cells are directly involved in the detection of touch. By creating a mouse strain that lacked the Atoh1 gene, and therefore lacked Merkel cells in the skin (while preserving the nerves that supply the skin), the team speculated they could determine whether Merkel cells participate in the sensation of touch. They tested this hypothesis by measuring neural activity in combined skin and nerve preparations isolated from the affected mice. When the scientists compared the electrical responses that the nerve endings produced against known electrical signatures for various types of sensory stimuli, they found that a specific response to light touch was missing, demonstrating that Merkel cells play a critical role in the detection of light touch stimuli.
The researchers hope their work will aid both skin and sensory research, and that their discovery about the origins of Merkel cells will advance research on Merkel cell carcinoma, a rare and aggressive skin cancer for which there are no effective treatments.
The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), a part of the U.S. 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 http://www.niams.nih.gov.
Morrison K, Miesegaes G, Lumpkin E, Maricich S. Mammalian Merkel cells are descended from the epidermal lineage. Dev Biol. 2009 Dec 1;336(1):76-83.
Maricich S, Wellnitz S, Nelson A, Lesniak D, Gerling G, Lumpkin E, Zoghbi H. Merkel cells are essential for light-touch responses. Science. 2009 Jun 19;324(5934):1580-2.