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 dur ing development. There is consensus that many of the NGF-dependent neu rons are small-diameter, peptidergic neurons subserving nociception. T hese neurons express the signaling receptor for NGF, TrkA. There is a major discrepancy, however, between the percentage of DRG neurons whic h require NGF for survival (70-85%) and percentage of DRG neurons expr essing TrkA receptors (40-50%). The identity of these non-TrkA express ing, NGF-dependent neurons has not been established. A candidate group is a population of small DRG neurons with unmyelinated axons which bi nd BSI isolectins from the plant, Bandeiraea simplicifolia. We show he re that most of these BSI-binding DRG neurons do not express TrkA in a dult mice. However, in mutant mice in which NGF/TrkA signaling has bee n abolished by inactivation of the trkA gene, BSI-staining in the DRG and dorsal horn is completely eliminated. BSI-binding DRG cells are th us the first identified neuronal population in which cells do not expr ess TrkA in maturity, but require NGF/TrkA signaling for survival duri ng embryonic development. These neurons must either depend on NGF via a novel, indirect mechanism or alternatively, downregulate TrkA expres sion during development.