Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia

Abstract

All members of the neurotrophin family of neuronal growth factors promote survival and neurite outgrowth of dorsal root ganglion (DRG) neurons in vitro. The trk family of protooncogenes encodes receptors that are now thought to mediate the biological effects of neurotrophins. In order to learn more about the dependence of DRG neurons on neurotrophins in vivo, we have studied mRNA expression of members of the trk family in developing DRGs in embryonic and postnatal rats. We show here that neurotrophin receptors are expressed in thoracic and lumbar DRGs by embryonic day 13 (E13), which is only 24-48 hr after neurogenesis begins in these ganglia. Distinct patterns of expression of trkA, trkB, and 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 change little between E15 and postnatal day 1. Although absolute numbers of DRG neurons expressing neurotrophin receptors are greater in lumbar than in thoracic ganglia, the ratios of DRG neurons expressing different members of the trk family are similar in the two regions. The different trks are expressed by distinct populations of DRG neurons from E15 onward. trkA is expressed predominantly by small neurons with darkly staining cytoplasm. trkB and trkC are expressed by large, lightly staining neurons. Size-frequency histograms show that trkA is expressed by neurons of variable sizes, but particularly by neurons at the smallest end of the spectrum. In contrast, trkC is expressed predominantly by large DRG neurons, including those with the largest soma areas. trkB is expressed by DRG neurons of intermediate size. Our results show that a majority of DRG neurons express mRNA for at least one member of the trk protooncogene family. Furthermore, trk expression occurs in a time frame consistent with the idea that trks mediate responses of DRG neurons to neurotrophins that are synthesized in both the periphery and spinal cord at early developmental stages. Finally, different populations of DRG neurons express different trks. We hypothesize that DRG neurons subserving different functions express different trks, and that trk expression of a particular class of DRG neurons determines its neurotrophin dependence during development.

Transient expression of the bHLH factor neurogenin-2 marks a subpopulation of neural crest cells biased for a sensory but not a neuronal fate

“…A much smaller proportion of lacZ ϩ cells appeared to be trkB ϩ or trkC ϩ (Fig. 4 C-F, arrows), consistent with the fact that these receptors are expressed by a smaller proportion of all sensory neurons at this stage (27). Thus, these data suggest that Ngn2-expressing NCCs contribute to multiple classes of sensory neurons in DRG, without any apparent bias toward a particular subtype.…”

“…4 A and B, arrows; n ϭ 10 embryos), a number remarkably close to the percentage of all neurons that express the receptor at this stage (Ϸ70%; ref. 27). A much smaller proportion of lacZ ϩ cells appeared to be trkB ϩ or trkC ϩ (Fig.…”

Rapid Axoglial Signaling Mediated by Neuregulin and Neurotrophic Factors

“…This occurs in a dose-dependent manner, is saturable, and occurs in a cell-specific way so that motor and sensory neurons have differential spectra of responsiveness to different neurotrophic factors. This is not surprising, because each type of neuron expresses a distinct spectrum of neurotrophic factor receptors (Ernfors et al, 1993;Mu et al, 1993;McMahon et al, 1994;Wright and Snider, 1995;Baig and Khan, 1996;Bhattacharyya et al, 1997;Copray and Kernell, 2000;Rifkin et al, 2000). A similar amount of NRG was released with nearly identical kinetics after PKC activation with PMA, raising the possibility that neurotrophic factor-induced activation of PKC is responsible for NRG release from axons.…”

The Rabies Virus Glycoprotein Receptor p75 NTR Is Not Essential for Rabies Virus Infection

“…p75 NTR is strongly expressed in a subpopulation of DRG neurons (39,40). The p75 NTR -positive neurons are in themselves diverse and can be further distinguished by cell size (60) and the differential expression of tyrosine kinase (Trk) receptors (40), transient receptor potential (TRP) channels (26), or neu-ropeptides (32).…”

“…p75 NTR is strongly expressed in a subpopulation of DRG neurons (39,40). The p75 NTR -positive neurons are in themselves diverse and can be further distinguished by cell size (60) and the differential expression of tyrosine kinase (Trk) receptors (40), transient receptor potential (TRP) channels (26), or neu-ropeptides (32). TRP channels have emerged as main determinants for the functional heterogeneity of DRG neurons, and the capsaicin receptor TRPV1 is the crucial receptor in the pain pathway and conveniently allows in culture the separation of small-diameter nociceptive sensory neurons from large-diameter nonnociceptive neurons (8).…”