Researchers at the University of Pennsylvania, School of Medicine, Philadelphia, have pinpointed a molecular pathway that regulates the development of taste buds, according to a study in the January issue of Nature Genetics.
Using genetically engineered mice, the researchers discovered that a signaling pathway activated by small proteins called Wnts is required to initiate taste bud formation. They also determined that Wnt proteins are required for hooking up the wiring of taste signals to the brain.
The researchers demonstrated that blocking the action of Wnt proteins in surface cells of the developing tongue prevents the formation of taste buds, while stimulating Wnt activity causes the formation of excessive numbers of enlarged taste papillae that are able to attract taste-related nerve fibers.
Although this study was performed in mice, the researchers believe that their findings also will apply to our understanding of the basis of taste bud development in humans.
The signaling pathway activated by Wnt proteins is critical to the development of many organ systems, and its inappropriate activation causes human diseases, including colon cancer.
Using an enzymatic assay, researchers can visualize easily the sites of Wnt signaling in specially engineered transgenic mice. "We noticed in the tongue that there was this beautiful pattern of blue spots that correspond to the developing taste papillae," said senior author Sarah E. Millar, PhD, associate professor, Departments of Dermatology and Cell and Developmental Biology. "This connected the Wnt pathway to their development."
The researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, the tongues of mice in which Wnt signaling was overactivated were covered with many large papillae and taste buds.
"Unlike most surface epithelial cells, taste buds have characteristics of neurons as well as skin," said Dr. Millar. "Like other types of epithelial cells, they turn over and regenerate, but they also express chemo-receptors and make synapses with neurons."
The researchers studied how developing taste buds become wired into the nervous system. In early tongue development, neurons enter the tongue epithelium and make synapses with taste bud cells. This study confirmed that taste buds produce signals that attract nerve fibers to them. When the researchers prevented the development of taste buds by blocking Wnt signaling, the nerve fibers did not enter the tongue epithelium.
"They don’t know where to go on their own," Dr. Millar said.
Understanding the basis for the initiation of taste papilla formation, as well as the evolution and differences between species in the numbers and patterns of taste buds, can be more fully explored, explained Dr. Millar.
Future research will focus on determining whether Wnt signaling also is important for the periodic regeneration of taste buds from taste bud stem cells that occurs throughout life in adult animals. Taste bud regeneration can be affected by chemotherapy, so understanding this process will have important implications for patient care.
This research was supported by the National Institutes of Health.
