Absence of sensory neurons before target innervation in brain-derived neurotrophic factor-, neurotrophin 3-, and TrkC-deficient embryonic mice.
Gene-targeting experiments of Trk receptors and neurotrophins has confirmed the expectation that embryonic sensory and sympathetic neurons require neurotrophin function for survival. They have further revealed correlation between a specific neurotrophin requirement and eventual sensory modality. We have analyzed embryonic and neonatal mice with mutations in the BDNF, neurotrophin 3 (NT-3), and TrkC genes. Our data confirm an unexpectedly high proportion of sensory neuron losses in NT-3 (>70%), BDNF (>20%), and TrkC (>30%) mutants, which encompass populations thought to be NGF-dependent. Direct comparison of TrkC and NT-3 mutants indicates that only a subset of the NT-3-dependent neurons also requires TrkC. The observed losses in our TrkC mutant, which is null for all proteins encoded by the gene, are more severe than those previously reported for the kinase-negative TrkC mutation, implicating additional and important functions for the truncated receptors. Our data further indicate that mature NGF-requiring neurons undergo precocious and transitory requirements for NT-3 and/or BDNF. We suggest that neurotrophins may function in creating early heterogeneity that would enable ganglia to compensate for diverse modality requirements before the period of naturally occurring death.
Liebl
D J
DJ
Developmental Biology Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9133, USA.
Tessarollo
L
L
Palko
M E
ME
Parada
L F
LF
D000344:Afferent Pathways / Q000166:cytology / Q000196:embryology; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019070:Cell Lineage; D002470:Cell Survival; D003391:Cranial Nerves / Q000166:cytology / Q000201:enzymology*; D005154:Facial Nerve / Q000166:cytology / Q000196:embryology; D005260:Female; D017950:Ganglia, Sensory / Q000166:cytology / Q000196:embryology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009046:Motor Neurons / Q000166:cytology; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology; D009475:Neurons, Afferent / Q000166:cytology*; D020933:Neurotrophin 3; D009620:Nodose Ganglion / Q000166:cytology / Q000196:embryology; D009928:Organ Specificity; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013127:Spinal Nerves / Q000166:cytology / Q000196:embryology*; D013136:Spiral Ganglion / Q000166:cytology / Q000196:embryology; D012668:Trigeminal Ganglion / Q000166:cytology / Q000196:embryology; D014276:Trigeminal Nerve / Q000166:cytology / Q000196:embryology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D020933:Neurotrophin 3; D017475:Receptors, Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC