PMID- 10212310
OWN - NLM
STAT- MEDLINE
DCOM- 19990507
LR  - 20231014
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 19
IP  - 9
DP  - 1999 May 1
TI  - Role of brain-derived neurotrophic factor in target invasion in the gustatory 
      system.
PG  - 3507-18
AB  - 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.
FAU - Ringstedt, T
AU  - Ringstedt T
AD  - Laboratory of Molecular Neurobiology, Department of Neuroscience, Karolinska 
      Institutet, S-171 77 Stockholm, Sweden.
FAU - Ibanez, C F
AU  - Ibanez CF
FAU - Nosrat, C A
AU  - Nosrat CA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Intermediate Filament Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nes protein, mouse)
RN  - 0 (Nestin)
SB  - IM
MH  - Animals
MH  - Brain/physiology
MH  - Brain-Derived Neurotrophic Factor/deficiency/genetics/*physiology
MH  - Embryonic and Fetal Development
MH  - Gene Expression Regulation
MH  - Geniculate Ganglion/physiology
MH  - Intermediate Filament Proteins/genetics/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Microscopy, Electron, Scanning
MH  - Nerve Fibers/physiology
MH  - *Nerve Tissue Proteins
MH  - Nestin
MH  - Neurons/physiology
MH  - Organ Specificity
MH  - Reference Values
MH  - Regulatory Sequences, Nucleic Acid
MH  - Taste Buds/abnormalities/pathology/*physiology
MH  - Tongue/embryology/innervation/*physiology/ultrastructure
PMC - PMC6782244
EDAT- 1999/04/23 00:00
MHDA- 1999/04/23 00:01
PMCR- 1999/11/01
CRDT- 1999/04/23 00:00
PHST- 1999/04/23 00:00 [pubmed]
PHST- 1999/04/23 00:01 [medline]
PHST- 1999/04/23 00:00 [entrez]
PHST- 1999/11/01 00:00 [pmc-release]
AID - 2985 [pii]
AID - 10.1523/JNEUROSCI.19-09-03507.1999 [doi]
PST - ppublish
SO  - J Neurosci. 1999 May 1;19(9):3507-18. doi: 10.1523/JNEUROSCI.19-09-03507.1999.