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Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate

Abstract

Tactile information is perceived by a heterogeneous population of specialized neurons. Neurotrophin receptors (the receptor tyrosine kinases, Trks) mark the major classes of these sensory neurons: TrkA is expressed in neurons that sense temperature and noxious stimuli, and TrkC is expressed in proprioceptive neurons that sense body position. Neurotrophin signaling through these receptors is required for cell survival. To test whether neurotrophins have an instructive role in sensory specification, we expressed rat TrkC from the TrkA (also known as Ntrk1) locus in mice. The surviving presumptive TrkA-expressing neurons adopted a proprioceptive phenotype, indicating that neurotrophin signaling can specify sensory neuron subtypes.

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Figure 1: Mice engineered to express TrkC protein from the TrkA locus.
Figure 2: Mice engineered to express tau-lacZ (τlacZ) fusion protein from the TrkA locus, while inactivating TrkA.
Figure 3: DRG neurons from TrkATrkC/TrkC mice do not express markers specific for the TrkA population, but a greater number of neurons express markers for the TrkC population.
Figure 4: Increased innervation of proprioceptive target tissues in TrkATrkC/TrkC mice.
Figure 5: Mechanism of the phenotypic switch in TrkATrkC/TrkC mice.

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References

  1. Scott, S.A. Sensory Neurons: Diversity, Development, and Plasticity (Oxford Univ. Press, New York, 1992).

    Google Scholar 

  2. Patapoutian, A. & Reichardt, L.F. Trk receptors: mediators of neurotrophin action. Curr. Opin. Neurobiol. 11, 272–280 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Huang, E.J. & Reichardt, L.F. Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24, 677–736 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Markus, A., Patel, T.D. & Snider, W.D. Neurotrophic factors and axonal growth. Curr. Opin. Neurobiol. 12, 523–531 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. Gundersen, R.W. & Barrett, J.N. Neuronal chemotaxis: chick dorsal-root axons turn toward high concentrations of nerve growth factor. Science 206, 1079–1080 (1979).

    Article  CAS  PubMed  Google Scholar 

  6. Song, H.J., Ming, G.L. & Poo, M.M. cAMP-induced switching in turning direction of nerve growth cones [published erratum appears in Nature 389, 412 (1997)]. Nature 388, 275–279 (1997).

    Article  CAS  PubMed  Google Scholar 

  7. Patapoutian, A., Backus, C., Kispert, A. & Reichardt, L.F. Regulation of neurotrophin-3 expression by epithelial-mesenchymal interactions: the role of Wnt factors. Science 283, 1180–1183 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Patel, T.D., Jackman, A., Rice, F.L., Kucera, J. & Snider, W.D. Development of sensory neurons in the absence of NGF/TrkA signaling in vivo. Neuron 25, 345–357 (2000).

    Article  CAS  PubMed  Google Scholar 

  9. Tucker, K.L., Meyer, M. & Barde, Y.A. Neurotrophins are required for nerve growth during development. Nat. Neurosci. 4, 29–37 (2001).

    Article  CAS  PubMed  Google Scholar 

  10. Patel, T.D. et al. Peripheral NT3 signaling is required for ETS protein expression and central patterning of proprioceptive sensory afferents. Neuron 38, 403–416 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Smeyne, R.J. et al. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene. Nature 368, 246–249 (1994).

    Article  CAS  PubMed  Google Scholar 

  12. Wright, D.E., Zhou, L., Kucera, J. & Snider, W.D. Introduction of a neurotrophin-3 transgene into muscle selectively rescues proprioceptive neurons in mice lacking endogenous neurotrophin-3. Neuron 19, 503–517 (1997).

    Article  CAS  PubMed  Google Scholar 

  13. Caterina, M.J. et al. The capsaicin receptor: a heat-activated ion channel in the pain pathway [see comments]. Nature 389, 816–824 (1997).

    Article  CAS  PubMed  Google Scholar 

  14. McKemy, D.D., Neuhausser, W.M. & Julius, D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416, 52–58 (2002).

    Article  CAS  PubMed  Google Scholar 

  15. Peier, A.M. et al. A TRP channel that senses cold stimuli and menthol. Cell 108, 705–715 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Arber, S., Ladle, D.R., Lin, J.H., Frank, E. & Jessell, T.M. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell 101, 485–498 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. Aloe, L. & Levi-Montalcini, R. Nerve growth factor-induced transformation of immature chromaffin cells in vivo into sympathetic neurons: effect of antiserum to nerve growth factor. Proc. Natl. Acad. Sci. USA 76, 1246–1250 (1979).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. O'Connor, R., & Tessier-Lavigne, M. Identification of maxillary factor, a maxillary process-derived chemoattractant for developing trigeminal sensory axons. Neuron. 24, 165–178 (1999).

    Article  CAS  PubMed  Google Scholar 

  19. Chen, Z.F. et al. The paired homeodomain protein DRG11 is required for the projection of cutaneous sensory afferent fibers to the dorsal spinal cord. Neuron 31, 59–73 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Lin, J.H. et al. Functionally related motor neuron pool and muscle sensory afferent subtypes defined by coordinate ETS gene expression. Cell 95, 393–407 (1998).

    Article  CAS  PubMed  Google Scholar 

  21. Inoue, K. et al. Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons. Nat. Neurosci. 5, 946–954 (2002).

    Article  CAS  PubMed  Google Scholar 

  22. Tsoulfas, P. et al. The rat trkC locus encodes multiple neurogenic receptors that exhibit differential response to neurotrophin-3 in PC12 cells. Neuron 10, 975–990 (1993).

    Article  CAS  PubMed  Google Scholar 

  23. Swiatek, P.J. & Gridley, T. Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes Dev. 7, 2071–2084 (1993).

    Article  CAS  PubMed  Google Scholar 

  24. Leu, M. et al. ErbB2 regulates neuromuscular synapse formation and is essential for muscle spindle development. Development 130, 2291–2301 (2003).

    Article  CAS  PubMed  Google Scholar 

  25. Story, G.M. et al. ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 112, 819–829 (2003).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank S. Arber, M. Barbacid, P. Mombaerts, P. Tsoulfas, B. Wold and J. Yoon for reagents; S. Kupriyanov and G. Story for assistance; and S. Halpain, N. Hong, U. Mueller and L. Stowers for critical reading of the manuscript. This work was mainly supported by a National Institute of Neurological Disorders and Stroke grant (5R01NS42822 to A.P.). Other support included: Basil O'Connor Starter Scholar Research Award to A.P., NIH P01-16033 to L.F.R., NIH R29NS37910 to D.E.W., and Spanish Ministry of Science and Technology grant (PM99-0118) to D.M.Z. A.P. is a Damon Runyon Scholar. L.F.R. is an investigator of the Howard Hughes Medical Institute.

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Correspondence to Ardem Patapoutian.

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Moqrich, A., Earley, T., Watson, J. et al. Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate. Nat Neurosci 7, 812–818 (2004). https://doi.org/10.1038/nn1283

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