Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons

Cell. 1995 Sep 8;82(5):733-42. doi: 10.1016/0092-8674(95)90470-0.


Mutations at the neurofibromatosis 1 (NF1) locus in humans and mice result in abnormal growth of neural crest-derived cells, including melanocytes and Schwann cells. We have exploited a targeted disruption of the NF1 gene in mice to examine the role of neurofibromin in the acquisition of neurotrophin dependence in embryonic neurons. We show that both neural crest- and placode-derived sensory neurons isolated from NF1(-/-) embryos develop, extend neurites, and survive in the absence of neurotrophins, whereas their wild-type counterparts die rapidly unless nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF) is added to the culture medium. Moreover, NF1 (-/-) sympathetic neurons survive for extended periods and acquire mature morphology in the presence of NGF-blocking antibodies. Our results are consistent with a model wherein neurofibromin acts as a negative regulator of neurotrophin-mediated signaling for survival of embryonic peripheral neurons.

Publication types

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

MeSH terms

  • Animals
  • Axons / physiology
  • Cell Survival / genetics
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / physiology
  • Genes, Neurofibromatosis 1 / genetics*
  • Mice
  • Mice, Inbred Strains
  • Mutation / genetics
  • Nerve Growth Factors / physiology*
  • Neurofibromin 1
  • Neurons, Afferent / cytology
  • Neurons, Afferent / physiology*
  • Neurons, Afferent / ultrastructure
  • Proteins / genetics*
  • Sympathetic Nervous System / cytology
  • Sympathetic Nervous System / embryology
  • Sympathetic Nervous System / physiology*
  • Trigeminal Nuclei / cytology


  • Nerve Growth Factors
  • Neurofibromin 1
  • Proteins