The Journal of Neuroscience, May 1, 1999, 19(9):3507-3518
Role of Brain-Derived Neurotrophic Factor in Target Invasion
in the Gustatory System
Thomas
Ringstedt,
Carlos F.
Ibáñez, and
Christopher A.
Nosrat
Laboratory of Molecular Neurobiology, Department of Neuroscience,
Karolinska Institutet, S-171 77 Stockholm, Sweden
Brain-derived neurotrophic factor (BDNF) is a survival factor for
different classes of neurons, including gustatory neurons. We have
studied innervation and development of the gustatory system in
transgenic mice overexpressing BDNF under the
control of regulatory sequences from the nestin gene, an
intermediate filament gene expressed in precursor cells of the
developing nervous system and muscle. In transgenic mice, the number
and size of gustatory papillae were decreased, circumvallate papillae
had a deranged morphology, and there was also a severe loss of lingual
taste buds. Paradoxically, similar deficits have been found in BDNF knock-out mice, which lack gustatory neurons. However, the number of
neurons in gustatory ganglia was increased in BDNF-overproducing mice.
Although gustatory fibers reached the tongue in normal numbers, the
amount and density of nerve fibers in gustatory papillae were reduced
in transgenic mice compared with wild-type littermates. Gustatory
fibers appeared stalled at the base of the tongue, a site of ectopic
BDNF expression, where they formed abnormal branches and
sprouts. Interestingly, palatal taste buds, which are innervated by
gustatory neurons whose afferents do not traverse sites of ectopic BDNF
expression, appeared unaffected. We suggest that lingual gustatory
deficits in BDNF overexpressing mice are a consequence of the failure
of their BDNF-dependent afferents to reach their targets because of the
effects of ectopically expressed BDNF on fiber growth.
Our findings suggest that mammalian taste buds and gustatory papillae
require proper BDNF-dependent gustatory innervation for development and
that the correct spatial expression of BDNF in the
tongue epithelium is crucial for appropriate target invasion and innervation.
Key words:
taste buds; gustatory; neurotrophins; gustation; transgenic; innervation
Copyright © 1999 Society for Neuroscience 0270-6474/99/1993507-12$05.00/0
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