NEUROTROPHIN RECEPTOR MESSENGER-RNA EXPRESSION DEFINES DISTINCT POPULATIONS OF NEURONS IN RAT DORSAL-ROOT GANGLIA

The biological actions of neurotrophins are mediated by specific neuro trophin receptor tyrosine kinases (Trks). A low-affinity nerve growth factor (NGF) receptor, p75, appears to modulate sensitivity to neurotr ophins in some neuronal populations. It has been recently demonstrated that genes encoding members of the Trk family are expressed in distin ct patterns in the dorsal root ganglia (DRG; Mu et al. [1993] (J. Neur osci. 13:4029-4041). However, the extent to which different neurotroph in receptor genes are coexpressed by individual DRG neurons is unknown . The question of coexpression is important since the expression of mo re than one member of the trh family by DRG neurons would suggest the potential for regulation by multiple neurotrophins. To address this qu estion, a combination of isotopic and colorimetric in situ hybridizati on was performed on rat thoracic DRG using riboprobes specific for trk A, trkB, trkC, and p75. We show here that neurons that express trkA ar e largely distinct from those that express trkC, although there is a s mall subpopulation that expresses both of these genes. We also show th at there is a distinct population of DRG neurons that expresses trkB a nd does not coexpress either trkA or trkC. P75 is expressed in almost all neurons that express trkA or trkB, but is coexpressed in only 50% of trkC-expressing neurons. Importantly, p75 is not expressed in DRG n eurons independent of trk expression. Finally, a subpopulation of DRG neurons does not express any of the neurotrophin receptor mRNAs. Our r esults demonstrate that there are distinct populations of DRG neurons that express each member of the neurotrophin receptor tyrosine kinase family. Our findings of extensive colocalization of p75 with trkA and trkB lend support to the idea that p75 is important in mediating the a ctions of NGF and brain-derived neurotrophic factor on DRG neurons. In terestingly, however, p75 expression is clearly unimportant for a subp opulation of neurons that require neurotrophin-3. The fact that p75 is not expressed in the absence of trkA, trkB, or trkC suggests that the function of p75 is closely related to functions of the known neurotro phin receptor tyrosine kinases. Finally, our results suggest that a si gnificant percentage of DRG neurons may be regulated by non-neurotroph in neuronal growth factors. (C) 1995 Wiley-Liss, Inc.