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Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons

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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Figure 1: Expression of Runx3 in mice embryo.
Figure 2: Biochemical properties of DRG neurons in Runx3−/− mice.
Figure 3: Absence of proprioceptive afferent projections to the motor pools in Runx3−/− mice.
Figure 4: Unchanged neuronal cell fate and survival of trkC-expressing neurons in Runx3−/− DRGs.
Figure 5: Defects in proprioceptive afferent projections to the spinal cord in Runx3−/− embryos.
Figure 6: Defects in peripheral nerve innervation of proprioceptive DRG neurons in Runx3−/− mice.
Figure 7: Neurite outgrowth from Runx3−/− DRG neurons in explant culture.
Figure 8: Motor discoordination in Runx3−/− adult mice with ICR background.

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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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Correspondence to Yoshiaki Ito.

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Inoue, Ki., Ozaki, S., Shiga, T. et al. Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons. Nat Neurosci 5, 946–954 (2002). https://doi.org/10.1038/nn925

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