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Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons

Nature Neuroscience volume 5, pages 946954 (2002) | Download Citation

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Abstract

Dorsal root ganglion (DRG) neurons specifically project axons to central and peripheral targets according to their sensory modality. The Runt-related genes Runx1 and Runx3 are expressed in DRG neuronal subpopulations, suggesting that they may regulate the trajectories of specific axons. Here we report that Runx3-deficient (Runx3−/−) mice displayed severe motor discoordination and that few DRG neurons synthesized the proprioceptive neuronal marker parvalbumin. Proprioceptive afferent axons failed to project to their targets in the spinal cord as well as those in the muscle. NT-3-responsive Runx3−/− DRG neurons showed less neurite outgrowth in vitro. However, we found no changes in the fate specification of Runx3−/− DRG neurons or in the number of DRG neurons that expressed trkC. Our data demonstrate that Runx3 is critical in regulating the axonal projections of a specific subpopulation of DRG neurons.

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Acknowledgements

We thank U. Banerjee for communicating data before publication and for discussions, L.F. Reichardt for the gift of the TrkA and TrkC antibodies, M. Yamamoto for reading the manuscript, I. Matsumoto and K. Abe for the trkC plasmids, and K. Takeuchi, T. Iwasato and J. Sakamoto for technical assistance. This work was supported in part by Grant for Priority Areas in Cancer Research and Grant for Scientific Research (A) to Y.I. from the Ministry of Education, Culture, Sports, Science and Technology of Japan. Ken. I, Ko. I, N.Y. and Y.I. are currently supported by A*STAR (Agency for Science, Technology and Research), Singapore.

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Author notes

    • Ken-ichi Inoue
    •  & Shigeru Ozaki

    The first two authors contributed equally to this work

Affiliations

  1. Laboratory of Cell Regulation, Department of Viral Oncology, Institute for Virus Research, Kyoto University, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan

    • Ken-ichi Inoue
    • , Kosei Ito
    • , Namiko Yamashita
    •  & Yoshiaki Ito
  2. Department of Physiology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan

    • Shigeru Ozaki
    •  & Norio Kudo
  3. Department of Anatomy, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan

    • Takashi Shiga
    • , Tomoyuki Masuda
    •  & Nobuo Okado
  4. Department of Integrative Brain Science, Graduate School of Medicine, Kyoto University, Konoe, Yoshida, Kyoto 606-8501, Japan

    • Tsutomu Iseda
    •  & Saburo Kawaguchi
  5. Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan

    • Masaharu Ogawa
  6. Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, Cheongju, 361-763, South Korea

    • Suk-Chul Bae
  7. Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, Wako, Saitama 351-0198, Japan

    • Shigeyoshi Itohara
  8. Institute of Molecular and Cell Biology, 30 Medical Drive, Singapore 117609, Singapore

    • Ken-ichi Inoue
    • , Kosei Ito
    • , Namiko Yamashita
    •  & Yoshiaki Ito

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The authors declare no competing financial interests.

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Correspondence to Yoshiaki Ito.

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DOI

https://doi.org/10.1038/nn925

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