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 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.
Ringstedt
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Laboratory of Molecular Neurobiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Ibáñez
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Nosrat
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D000818:Animals; D001921:Brain / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005314:Embryonic and Fetal Development; D005786:Gene Expression Regulation; D005830:Geniculate Ganglion / Q000502:physiology; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D009412:Nerve Fibers / Q000502:physiology; D009419:Nerve Tissue Proteins; D064231:Nestin; D009474:Neurons / Q000502:physiology; D009928:Organ Specificity; D012016:Reference Values; D012045:Regulatory Sequences, Nucleic Acid; D013650:Taste Buds / Q000002:abnormalities / Q000473:pathology / Q000502:physiology*; D014059:Tongue / Q000196:embryology / Q000294:innervation / Q000502:physiology* / Q000648:ultrastructure
D019208:Brain-Derived Neurotrophic Factor; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin