PMID- 11684666
OWN - NLM
STAT- MEDLINE
DCOM- 20011226
LR  - 20220215
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 128
IP  - 21
DP  - 2001 Nov
TI  - Dissection of NT3 functions in vivo by gene replacement strategy.
PG  - 4315-27
AB  - The development of the peripheral nervous system is governed in part by a family 
      of neurotrophic factors that signal through Trk tyrosine kinase receptors. 
      Neurotrophin 3 (NT3) ablation in mice causes a more severe neuronal phenotype 
      than deletion of its receptor TrkC, suggesting that NT3 acts also through other 
      non-preferred Trk receptors. To study the role of low-affinity ligand receptor 
      interactions in vivo, we have replaced the Nt3 gene with the gene for 
      brain-derived neurotrophic factor (BDNF), a TrkB ligand. As in NT3 and TrkC null 
      mice, the proprioception system of these mutants failed to assemble. However, 
      sensory fiber projections in the embryonic spinal cord suggest chemotropic 
      effects of BDNF in vivo. In the dorsal root ganglia, the developmental dynamic of 
      neuron numbers demonstrates that NT3 is required for activation of TrkB during 
      neurogenesis and that TrkA is required during target tissue innervation. In the 
      inner ear, the ectopic BDNF rescued the severe neuronal deficits caused by NT3 
      absence, indicating that TrkB and TrkC activate equivalent pathways to promote 
      survival of cochlear neurons. However, specific increased innervation densities 
      suggest unique functions for BDNF and NT3 beyond promoting neuronal survival. 
      This mouse model has allowed the dissection of specific spatiotemporal Trk 
      receptor activation by NT3. Our analysis provides examples of how development can 
      be orchestrated by complex high- and low-affinity interactions between ligand and 
      receptor families.
FAU - Coppola, V
AU  - Coppola V
AD  - Neural Development Group, Mouse Cancer Genetics Program, NCI, Frederick, MD 
      21701, USA.
FAU - Kucera, J
AU  - Kucera J
FAU - Palko, M E
AU  - Palko ME
FAU - Martinez-De Velasco, J
AU  - Martinez-De Velasco J
FAU - Lyons, W E
AU  - Lyons WE
FAU - Fritzsch, B
AU  - Fritzsch B
FAU - Tessarollo, L
AU  - Tessarollo L
LA  - eng
GR  - 2 P01 DC00215/DC/NIDCD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
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
EIN - Development 2003 Jan;130(1):233
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/metabolism
MH  - Ear, Inner/embryology/innervation
MH  - Female
MH  - Ganglia, Spinal/cytology/*embryology
MH  - Genetic Techniques
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Neurons, Afferent/metabolism/pathology
MH  - Neurotrophin 3/*physiology
MH  - Receptor, trkB/genetics/metabolism
MH  - Receptor, trkC/genetics/metabolism
MH  - Spinal Cord/cytology/embryology
EDAT- 2001/10/31 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/31 10:00
PHST- 2001/10/31 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/31 10:00 [entrez]
AID - 10.1242/dev.128.21.4315 [doi]
PST - ppublish
SO  - Development. 2001 Nov;128(21):4315-27. doi: 10.1242/dev.128.21.4315.