Research team discovers origin of Merkel cells

A 130-year-old mystery has been solved that could provide more insight into a rare form of skin cancer: Merkel cells originate in the skin, not the neural crest lineage as previously thought.

The discovery was made by a research team headed by Stephen M. Maricich, M.D., Ph.D., assistant professor of pediatrics, neurosciences and otolaryngology at the Case Western Reserve University School of Medicine.

Merkel cells, discovered by Friedrich Sigmund Merkel in 1875, are found in multiple regions of the skin and make contact with specialized nerve fibers, participating in the perception of touch.

"A real mystery surrounding Merkel cells was their developmental site of origin. Conflicting evidence suggested that these cells arose from either the skin or neural crest lineages, but there was no definite proof of either origin," said Maricich, lead author of the study.

"It is thought that Merkel cells give rise to Merkel cell carcinoma, a rare but aggressive form of skin cancer that responds poorly to current treatments," Maricich said. "In addition to solving a 130-year-old mystery, our data may be relevant to the understanding of Merkel cell carcinoma, and may provide important clues in the search for novel therapeutic targets."

Using genetically engineered mouse lines, the researchers were able to delete Atoh1, a gene essential to the formation of Merkel cells, from different areas of developing embryos. This "conditional deletion" of Atoh1 in the neural crest did not affect the Merkel cell population. However, using this same technique in the skin lineage resulted in the loss of all Merkel cells.

"Knocking out Atoh1 in the neural crest line caused other problems for developing embryos, but Merkel cells were completely unaffected. However, loss of Atoh1 expression in the skin deleted all the Merkel cells," said Maricich. "This showed us that we had specifically targeted the Merkel cells and that Atoh1 expression by skin cells is necessary to their development."

The researchers also fate mapped the cells, a technique used to trace developmental fates of embryonic tissues. This analysis further supported their conditional knockout findings.

The study, "Mammalian Merkel Cells are Descended from the Epidermal Lineage," was recently published in the online version of Developmental Biology and is slated for its future print edition.

Funding for this study came from the National Institute of Neurological Disorders and Stroke and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Both are of the National Institutes of Health.