PMID- 11487640
OWN - NLM
STAT- MEDLINE
DCOM- 20010830
LR  - 20210910
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 21
IP  - 16
DP  - 2001 Aug 15
TI  - Spatial shaping of cochlear innervation by temporally regulated neurotrophin 
      expression.
PG  - 6170-80
AB  - Previous work suggested qualitatively different effects of neurotrophin 3 (NT-3) 
      in cochlear innervation patterning in different null mutants. We now show that 
      all NT-3 null mutants have a similar phenotype and lose all neurons in the basal 
      turn of the cochlea. To understand these longitudinal deficits in neurotrophin 
      mutants, we have compared the development of the deficit in the NT-3 mutant to 
      the spatial-temporal expression patterns of brain-derived neurotrophic factor 
      (BDNF) and NT-3, using lacZ reporters in each gene and with expression of the 
      specific neurotrophin receptors, trkB and trkC. In the NT-3 mutant, almost normal 
      numbers of spiral ganglion neurons form, but fiber outgrowth to the basal turn is 
      eliminated by embryonic day (E) 13.5. Most neurons are lost between E13.5 and 
      E15.5. During the period preceding apoptosis, NT-3 is expressed in supporting 
      cells, whereas BDNF is expressed mainly in hair cells, which become postmitotic 
      in an apical to basal temporal gradient. During the period of neuronal loss, BDNF 
      is absent from the basal cochlea, accounting for the complete loss of basal turn 
      neurons in the NT-3 mutant. The spatial gradients of neuronal loss in these two 
      mutants appear attributable to spatial-temporal gradients of neurotrophin 
      expression. Our immunocytochemical data show equal expression of their receptors, 
      TrkB and TrkC, in spiral sensory neurons and thus do not relate to the basal turn 
      loss. Mice in which NT-3 was replaced by BDNF show a qualitative normal pattern 
      of innervation at E13.5. This suggests that the pattern of expression of 
      neurotrophins rather than their receptors is essential for the spatial loss of 
      spiral sensory neurons in NT-3 null mutants.
FAU - Farinas, I
AU  - Farinas I
AD  - Program in Neuroscience, Department of Physiology and Howard Hughes Medical 
      Institute, University of California, San Francisco, California 94143-0724, USA.
FAU - Jones, K R
AU  - Jones KR
FAU - Tessarollo, L
AU  - Tessarollo L
FAU - Vigers, A J
AU  - Vigers AJ
FAU - Huang, E
AU  - Huang E
FAU - Kirstein, M
AU  - Kirstein M
FAU - de Caprona, D C
AU  - de Caprona DC
FAU - Coppola, V
AU  - Coppola V
FAU - Backus, C
AU  - Backus C
FAU - Reichardt, L F
AU  - Reichardt LF
FAU - Fritzsch, B
AU  - Fritzsch B
LA  - eng
GR  - P 50 DC 00215/DC/NIDCD NIH HHS/United States
GR  - KO1 NS01872/NS/NINDS NIH HHS/United States
GR  - WT_/Wellcome Trust/United Kingdom
GR  - P50 MH048200-100005/MH/NIMH NIH HHS/United States
GR  - 48200/PHS HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
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 (Neurotrophin 3)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (Receptor, trkC)
SB  - IM
MH  - Afferent Pathways/cytology/embryology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/biosynthesis/genetics
MH  - Cell Count
MH  - Cell Survival/genetics
MH  - Cochlea/embryology/*innervation/*metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - Genes, Reporter
MH  - Heterozygote
MH  - Homozygote
MH  - Immunohistochemistry
MH  - Lac Operon
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mutation
MH  - Neurons, Afferent/cytology/metabolism
MH  - Neurotrophin 3/*biosynthesis/*genetics
MH  - Phenotype
MH  - Receptor, trkB/biosynthesis
MH  - Receptor, trkC/biosynthesis
MH  - Spiral Ganglion/cytology/embryology
PMC - PMC2710117
MID - NIHMS112795
EDAT- 2001/08/07 10:00
MHDA- 2001/08/31 10:01
PMCR- 2002/02/15
CRDT- 2001/08/07 10:00
PHST- 2001/08/07 10:00 [pubmed]
PHST- 2001/08/31 10:01 [medline]
PHST- 2001/08/07 10:00 [entrez]
PHST- 2002/02/15 00:00 [pmc-release]
AID - 21/16/6170 [pii]
AID - 5528 [pii]
AID - 10.1523/JNEUROSCI.21-16-06170.2001 [doi]
PST - ppublish
SO  - J Neurosci. 2001 Aug 15;21(16):6170-80. doi: 10.1523/JNEUROSCI.21-16-06170.2001.