Loss of brain-derived neurotrophic factor-dependent neural crest-derived sensory neurons in neurotrophin-4 mutant mice

Proc Natl Acad Sci U S A. 2000 Feb 29;97(5):2297-302. doi: 10.1073/pnas.040562597.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis
  • Biomarkers
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Count
  • Ganglia, Spinal / cytology
  • Gene Expression
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology*
  • Neural Crest / cytology*
  • Neurons, Afferent / cytology*
  • Receptor, trkB / biosynthesis

Substances

  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Nerve Growth Factors
  • Receptor, trkB
  • neurotrophin 4