Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice.
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.
Silos-Santiago
I
I
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Molliver
D C
DC
Ozaki
S
S
Smeyne
R J
RJ
Fagan
A M
AM
Barbacid
M
M
Snider
W D
WD
D000818:Animals; D001369:Axons / Q000648:ultrastructure; D002470:Cell Survival; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D006579:Heterozygote; D006720:Homozygote; D037102:Lectins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D009619:Nociceptors / Q000502:physiology; D010766:Phosphorylation; D037121:Plant Lectins; D020917:Receptor, trkA / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
C045475:Griffonia simplicifolia lectins; D037102:Lectins; D016900:Neurofilament Proteins; D009479:Neuropeptides; D037121:Plant Lectins; C051774:neurofilament protein H; D020917:Receptor, trkA