- Of the five senses, taste is one of the least understood, but
now researchers at the University of Pennsylvania School
of Medicine have come one step closer to understanding
how the sense of taste develops. They have pinpointed a molecular
pathway that regulates the development of taste buds. Using genetically
engineered mice, they discovered that a signaling pathway activated
by small proteins called Wnts is required for initiating taste-bud
formation. They have also determined that Wnt proteins are required
for hooking up the wiring of taste signals to the brain.
Senior author Sarah E. Millar, PhD, Associate
Professor in the Departments of Dermatology and Cell and Developmental
Biology, Penn postdoctoral fellow Fei Liu, PhD,
and colleagues report their findings in the most recent online issue
of Nature Genetics. “The developmental biology of
taste is underexplored,” says Millar of her team’s impetus
for the study.
The researchers demonstrated that blocking the action of Wnt proteins
in surface cells of the developing tongue prevents taste-bud formation,
while stimulating Wnt activity causes the formation of excessive
numbers of enlarged taste papillae that are able to attract taste-related
nerve fibers. This study represents the first genetic analysis of
taste-organ initiation in mammals. While these studies were performed
in mice, the researchers believe that their findings will also hold
true for understanding the basis of taste-bud development in humans.
Taste buds are the sensory organs that transmit chemical stimuli
from food and other sources to nerve cells, which convey these signals
to the taste centers in the brain. Taste buds sit in the small bumps
in the surface and sides of the tongue called papillae.
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. In previous studies,
Millar and colleagues have shown that this pathway is essential
for initiating the formation of hair follicles and mammary glands
The sites of Wnt signaling are easily visualized in specially engineered
transgenic mice, using an enzymatic assay. “We noticed in
the tongue that there was this beautiful pattern of blue spots that
correspond to the developing taste papillae,” says Millar.
“This connected the Wnt pathway to their development.”
In the present study, the researchers found that in mice in which
the actions of Wnt proteins were blocked, taste papilla buds completely
failed to develop. Conversely, in mice in which Wnt signaling was
over activated, their tongues were covered with many and large papillae
and taste buds.
“Unlike most surface epithelial cells, taste buds have characteristics
of neurons as well as skin. Like other types of epithelial cells
they turn over and regenerate, but they also express chemoreceptors
and make synapses with neurons,” explains Millar. The group
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
taste-bud development was prevented by blocking Wnt signaling, the
nerve fibers did not enter the tongue epithelium.
“They don’t know where to go on their own,” she
Millar also mentions that by now understanding the basis for the
initiation of taste-papilla formation, the evolution and difference
between species in the numbers and patterns of taste buds can be
more fully explored. All animals that taste have taste buds, but
there are differences, for example humans have more (around 200)
taste papillae than mice, and they are arranged in a different pattern.
Future research directions will include determining whether Wnt
signaling is also 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
The research was supported by the National Institutes of Health.
In addition to Millar and Liu, co-authors on the paper are: Natalie
Gallant, Seshamma T. Reddy, and Thomas Andl, from Penn; Shoba Thirumangalathu
and Linda Barlow from the University of Colorado Health Sciences
Center; Steven Yang and Andrzej A. Dlugosz from the University of
Michigan; Cristi L. Stoick-Cooper and Randall T. Moon from the Howard
Hughes Medical Institute and University of Washington; and Makoto
M. Taketo from Kyoto University.
PENN Medicine is a $2.9 billion enterprise
dedicated to the related missions of medical education, biomedical
research, and high-quality patient care. PENN Medicine consists
of the University of Pennsylvania School of Medicine (founded in
1765 as the nation's first medical school) and the University of
Pennsylvania Health System.
Penn's School of Medicine is ranked #2 in the nation for receipt
of NIH research funds; and ranked #3 in the nation in U.S. News
& World Report's most recent ranking of top research-oriented
medical schools. Supporting 1,400 fulltime faculty and 700 students,
the School of Medicine is recognized worldwide for its superior
education and training of the next generation of physician-scientists
and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals,
all of which have received numerous national patient-care honors [Hospital
of the University of Pennsylvania; Pennsylvania Hospital, the nation's
first hospital; and Penn Presbyterian Medical Center]; a faculty practice
plan; a primary-care provider network; two multispecialty satellite
facilities; and home care and hospice.