Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons.
We have generated double mutant mice deficient in pairs of two different Trk receptors and have analysed the effects on survival and differentiation of dorsal root ganglion (DRG), inner ear cochlear and vestibular sensory neurons. In most combinations of mutant trk alleles, the defects observed in double compared to single mutant mice were additive. However, double homozygous trkA-/-;trkB-/- DRG and trkB-/-;trkC-/- vestibular neurons showed the same degree of survival as single trkA-/- and trkB-/- mice, respectively, suggesting that those neurons required both Trk signaling pathways for survival. In situ hybridisation analysis of DRG neurons of double mutant mice revealed differential expression of excitatory neuropeptides. Whereas calcitonin-gene-related peptide expression correlated with the trkA phenotype, substance P expression was detected in all combinations of double mutant mice. In the inner ear, TrkB- and TrkC-dependent neurons were shown to at least partially depend on each other for survival, most likely indirectly due to abnormal development of their common targets. This effect was not observed in DRGs, where neurons depending on different Trk receptors generally innervate different targets.
Minichiello
L
L
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Piehl
F
F
Vazquez
E
E
Schimmang
T
T
Hökfelt
T
T
Represa
J
J
Klein
R
R
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D002454:Cell Differentiation; D002470:Cell Survival; D003056:Cochlear Nerve / Q000196:embryology; D005727:Ganglia, Spinal / Q000196:embryology; D015870:Gene Expression; D017403:In Situ Hybridization; D051379:Mice; D008817:Mice, Mutant Strains; D009475:Neurons, Afferent / Q000502:physiology*; D017933:Peripheral Nervous System / Q000196:embryology*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D020801:Receptor, Ciliary Neurotrophic Factor; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*; D013373:Substance P / Q000235:genetics; D014725:Vestibular Nerve / Q000196:embryology
D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D013373:Substance P; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC; D015740:Calcitonin Gene-Related Peptide