http://www.eurekalert.org/bysubject/medicine.php

 Public release date: 5-Dec-2006
[ Print Article | E-mail Article | Close Window ]

Contact: Karen Kreeger
[log in to unmask]
215-349-5658
University of Pennsylvania School of Medicine 

Penn researchers discover initial steps in the development of taste
Wnt protein required for taste buds and wiring of taste signals to the brain

--------------------------------------------------------------------------------
 
--------------------------------------------------------------------------------

The pattern of active wnt protein (dark blue) follows the development of taste
papillae and buds in the tongue of a mouse.

Click here for more information. 
--------------------------------------------------------------------------------
 
(PHILADELPHIA) -- 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 in mice. 

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 says. 

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 patient care. 

###
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.

For this release and related image, go to: http://www.uphs.upenn.edu/news/

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.



--------------------------------------------------------------------------------
 [ Print Article | E-mail Article | Close Window ] 

  

-----------------------

To change your mail settings or leave the C-PALSY list, go here:

http://listserv.icors.org/SCRIPTS/WA-ICORS.EXE?SUBED1=c-palsy