Role of brain-derived neurotrophic factor in target invasion in the gustatory system

Brain-derived neurotrophic factor (BDNF) is a survival factor for different classes of neurons, including gustatory neurons. We have studied innervati on and development of the gustatory system in transgenic mice overexpressin g BDNF under the control of regulatory sequences from the nestin gene, an i ntermediate filament gene expressed in precursor cells of the developing ne rvous system and muscle. In transgenic mice, the number and size of gustato ry papillae were decreased, circumvallate papillae had a deranged morpholog y, and there was also a severe loss of lingual taste buds. Paradoxically, s imilar deficits have been found in BDNF knock-out mice, which lack gustator y neurons. However, the number of neurons in gustatory ganglia was increase d in BDNF-overproducing mice. Although gustatory fibers reached the tongue in normal numbers, the amount and density of nerve fibers in gustatory papi llae were reduced in transgenic mice compared with wild-type littermates. G ustatory fibers appeared stalled at the base of the tongue, a site of ectop ic BDNF expression, where they formed abnormal branches and sprouts, Intere stingly, palatal taste buds, which are innervated by gustatory neurons whos e afferents do not traverse sites of ectopic BDNF expression, appeared unaf fected. We suggest that lingual gustatory deficits in BDNF overexpressing m ice are a consequence of the failure of their BDNF-dependent afferents to r each 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 developmen t and that the correct spatial expression of BDNF in the tongue epithelium is crucial for appropriate target invasion and innervation.