Loss of brain-derived neurotrophic factor-dependent neural crest-derived sensory neurons in neurotrophin-4 mutant mice.
Peripheral ganglion neurons confer sensory information including touch, pain, temperature, and proprioception. Sensory modality is linked to specific neurotrophin (NTF) requirements. NT-3 supports survival of neurons that differentiate primarily into proprioceptors whereas nerve growth factor and brain-derived neurotrophic factor (BDNF) support subpopulations that transmit nociception and mechanoreception, respectively. We examined sensory neurons of gene-targeted mouse mutants at the NT-4, BDNF, NT-3, and TrkA loci. We show that NT-4 functions early in gangliogenesis, upstream of BDNF. In the absence of NT-4 function, BDNF-dependent, TrkB-expressing neurons fail to appear. The results are consistent with the model that precursor cells intended to become BDNF-dependent mechanoreceptors instead differentiate into NT-3-dependent proprioceptive neurons.
Liebl
D J
DJ
Center for Developmental Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75235-9133, USA.
Klesse
L J
LJ
Tessarollo
L
L
Wohlman
T
T
Parada
L F
LF
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D002452:Cell Count; D005727:Ganglia, Spinal / Q000166:cytology; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009414:Nerve Growth Factors / Q000235:genetics / Q000502:physiology*; D009432:Neural Crest / Q000166:cytology*; D009475:Neurons, Afferent / Q000166:cytology*; D020813:Receptor, trkB / Q000096:biosynthesis
D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020813:Receptor, trkB; C073922:neurotrophin 4