Gene key to taste bud development identified

September 30, 2006

DURHAM, N.C. -- Scientists have identified a gene that controls the development of taste buds.

The gene, SOX2, stimulates stem cells on the surface of the embryonic tongue and in the back of the mouth to transform into taste buds, according to the researchers. Stem cells are immature cells that can develop into several different cell types depending on what biochemical instructions they receive.

"Not only did we find that SOX2 is crucial for the development of taste buds, but we showed that the amount of SOX2 is just as important," said Brigid Hogan, Ph.D., chair of the Duke University Medical Center Department of Cell Biology and senior member of the research team. "If there isn't enough SOX2 present, or if there is too much, the stem cells will not turn into taste buds."

The researchers made their discovery in mice, but they believe the same process occurs in humans.

According to the researchers, the findings will help scientists better understand how the behavior of certain stem cells is controlled. The SOX2 gene is already known to be crucial in controlling whether embryonic stem cells remain undifferentiated and whether stem cells in the brain, eye and inner ear differentiate into specialized nerve cells.

Taste bud cells, much like skin cells, continually slough off and are replaced by new ones. So the new findings not only provide insights into the interactions between SOX2 and tongue stem cells during embryonic development, but also into how stem cells continue to operate in adults, the researchers said.

The researchers published the findings in the October 2006 issue of the journal Genes and Development. The work was supported by the National Institutes of Health.

Their findings were entirely serendipitous, Hogan said.

"In my laboratory, we were studying the role of SOX2 in the development of the lung, esophagus and the gut in embryonic mice" she said. "We were quite surprised when we accidentally found the gene's role to be so pronounced in the developing tongue."

The particular strain of mice that Hogan and her colleagues use had been developed by Larysa Pevny, Ph.D., a geneticist and developmental neurobiologist at the University of North Carolina at Chapel Hill, who is co-author with Hogan of the journal report.

In engineering her new mouse strain for studying stem cells in the nervous system, Pevny combined the SOX2 gene with another gene, derived from jellyfish, and inserted the combination into the animals' chromosomes. She selected the added gene for its capacity to produce a special protein, called enhanced green fluorescent protein, that glows green when exposed to ultraviolet light.

"When we shine light on tissue from these animals, any cell that is expressing SOX2 will fluoresce, or light up," Pevny explained. "This allows us to directly visualize those areas where SOX2 is active. It is a very powerful tool."

In their work, Hogan and her colleagues use this fluorescence marker as a tool for tracking the activity of SOX2 in the esophagus, among other sites. As they worked with the mice, they noticed that specific areas on the tongue and in the back of the mouth lit up, in addition to areas in the esophagus. Further studies, Hogan said, confirmed that SOX2 was present in high amounts during the development of taste buds.

In another set of experiments, Hogan's team used another variant of the mouse strain made by Pevny in which the SOX2 gene was altered to produce only low levels of SOX2. In these animals, the stem cells in the tongue were not transformed into taste buds, she said. Instead, the cells became the "scaly" cells that cover the surface the tongue and help to direct food to the back of the mouth.

The new findings could lead to a better understanding of developmental disorders of the gut caused by mutations in the human SOX2 gene, Hogan said. For example, babies with such mutations can develop a tracheoesophageal fistula, a condition in which there is an abnormal connection between the windpipe and throat that requires surgery for correction.

Cancer patients receiving chemotherapy or radiation therapy often report the loss of taste during treatments. These therapies target cells that are dividing, making them effective in killing cancer cells but also causing the unwanted side effect of killing taste buds. When the cancer treatments end, the taste buds gradually return, Hogan said.
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Tadashi Okubo, a former post-doctoral fellow in Hogan's lab and now at the National Institutes of Natural Sciences, was also part of the research team.

Duke University Medical Center

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