Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice

Inmaculada Silos-Santiago, Derek C. Molliver, Shigeru Ozaki, Richard J. Smeyne, Anne M. Fagan, Mariano Barbacid, William D. Snider

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Abstract

Experiments over the past decade in which NGF/TrkA signaling has been abolished by antibodies or targeted gene mutations have shown that 70-85% of dorsal root ganglion (DRG) neurons require NGF for survival during development. There is consensus that many of the NGF-dependent neurons are small-diameter, peptidergic neurons subserving nociception. These neurons express the signaling receptor for NGF, TrkA. There is a major discrepancy, however, between the percentage of DRG neurons which require NGF for survival (70-85%) and percentage of DRG neurons expressing TrkA receptors (40-50%). The identity of these non-TrkA expressing, NGF-dependent neurons has not been established. A candidate group is a population of small DRG neurons with unmyelinated axons which bind BSI isolectins from the plant, Bandeiraea simplicifolia. We show here that most of these BSI-binding DRG neurons do not express TrkA in adult mice. However, in mutant mice in which NGF/TrkA signaling has been abolished by inactivation of the trkA gene, BSI-staining in the DRG and dorsal horn is completely eliminated. BSI-binding DRG cells are thus the first identified neuronal population in which cells do not express TrkA in maturity, but require NGF/TrkA signaling for survival during embryonic development. These neurons must either depend on NGF via a novel, indirect mechanism or alternatively, downregulate TrkA expression during development.

Original languageEnglish
Pages (from-to)5929-5942
Number of pages14
JournalJournal of Neuroscience
Volume15
Issue number9
DOIs
StatePublished - Sep 1995

Keywords

  • DRG neurons
  • NGF
  • TrkA
  • cell death
  • dorsal horn
  • neurotrophin receptors

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    Silos-Santiago, I., Molliver, D. C., Ozaki, S., Smeyne, R. J., Fagan, A. M., Barbacid, M., & Snider, W. D. (1995). Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice. Journal of Neuroscience, 15(9), 5929-5942. https://doi.org/10.1523/jneurosci.15-09-05929.1995