Neurotrophin receptor genes are expressed in distinct patterns in developing dorsal root ganglia.
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.
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Department of Neurology, Washington University Medical School, St. Louis, Missouri 63110.
Silos-Santiago
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Carroll
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Snider
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D000375:Aging / Q000378:metabolism*; D000818:Animals; D005314:Embryonic and Fetal Development; D005260:Female; D005727:Ganglia, Spinal / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D005786:Gene Expression Regulation; D005865:Gestational Age; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D005810:Multigene Family; D009414:Nerve Growth Factors / Q000378:metabolism*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D015513:Oncogene Proteins / Q000096:biosynthesis*; D011247:Pregnancy; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis; D020801:Receptor, Ciliary Neurotrophic Factor; D020917:Receptor, trkA; D020812:Receptor, trkC; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis
D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D015347:RNA Probes; D012333:RNA, Messenger; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C065400:oncogene protein trk; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA; D020812:Receptor, trkC