NEUROTROPHIN RECEPTOR GENES ARE EXPRESSED IN DISTINCT PATTERNS IN DEVELOPING DORSAL-ROOT GANGLIA

All members of the neurotrophin family of neuronal growth factors prom ote survival and neurite outgrowth of dorsal root ganglion (DRG) neuro ns in vitro. The trk family of protooncogenes encodes receptors that a re now thought to mediate the biological effects of neurotrophins. In order to learn more about the dependence of DRG neurons on neurotrophi ns in vivo, we have studied mRNA expression of members of the trk fami ly in developing DRGs in embryonic and postnatal rats. We show here th at neurotrophin receptors are expressed in thoracic and lumbar DRGs by embryonic day 13 (E13), which is only 24-48 hr after neurogenesis beg ins in these ganglia. Distinct patterns of expression of trkA, trkB, a nd trkC are readily apparent by E15. At this age, 40% of thoracic DRG neurons express trkA. In contrast, trkB and trkC are expressed by only 6% and 8%, respectively, of thoracic DRG neurons. These percentages c hange little between E15 and postnatal day 1. Although absolute number s of DRG neurons expressing neurotrophin receptors are greater in lumb ar than in thoracic ganglia, the ratios of DRG neurons expressing diff erent members of the trk family are similar in the two regions. The di fferent trks are expressed by distinct populations of DRG neurons from E15 onward. trkA is expressed predominantly by small neurons with dar kly staining cytoplasm. trkB and trkC are expressed by large, lightly staining neurons. Size-frequency histograms show that trkA is expresse d by neurons of variable sizes, but particularly by neurons at the sma llest end of the spectrum. In contrast, trkC is expressed predominantl y by large DRG neurons, including those with the largest soma areas. t rkB is expressed by DRG neurons of intermediate size. Our results show that a majority of DRG neurons express mRNA for at least one member o f the trk protooncogene family. Furthermore, trk expression occurs in a time frame consistent with the idea that trks mediate responses of D RG neurons to neurotrophins that are synthesized in both the periphery and spinal cord at early developmental stages. Finally, different pop ulations of DRG neurons express different trks. We hypothesize that DR G neurons subserving different functions express different trks, and t hat trk expression of a particular class of DRG neurons determines its neurotrophin dependence during development.