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

Kristine S Vogel, Camilynn I. Brannan, Nancy A. Jenkins, Neal G. Copeland, Luis F. Parada

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)733-742
Number of pages10
JournalCell
Volume82
Issue number5
DOIs
StatePublished - Sep 8 1995
Externally publishedYes

Fingerprint

Neurofibromin 1
Neurofibromatosis 1
Nerve Growth Factors
Sensory Receptor Cells
Neurons
Neural Crest
Nerve Growth Factor
Neurofibromatosis 1 Genes
Blocking Antibodies
Melanocytes
Schwann Cells
Brain-Derived Neurotrophic Factor
Neurites
Culture Media
Embryonic Structures
Mutation
Genes
Cells
Growth

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology
  • Molecular Biology

Cite this

Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons. / Vogel, Kristine S; Brannan, Camilynn I.; Jenkins, Nancy A.; Copeland, Neal G.; Parada, Luis F.

In: Cell, Vol. 82, No. 5, 08.09.1995, p. 733-742.

Research output: Contribution to journalArticle

Vogel, Kristine S ; Brannan, Camilynn I. ; Jenkins, Nancy A. ; Copeland, Neal G. ; Parada, Luis F. / Loss of neurofibromin results in neurotrophin-independent survival of embryonic sensory and sympathetic neurons. In: Cell. 1995 ; Vol. 82, No. 5. pp. 733-742.
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AU - Parada, Luis F.

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