Dynamic regulation of the expression of neurotrophin receptors by Runx3

Sensory neurons in the dorsal root ganglion (DRG) specifically project axons to central and peripheral targets according to their sensory modality. However, the molecular mechanisms that govern sensory neuron differentiation and the axonal projections remain unclear. The Runt-related transcription factors, Runx1 and Runx3, are expressed in DRG neuronal subpopulations, suggesting that they might regulate the cell specification and the trajectories of specific axons. Here, we show that parvalbumin-positive DRG neurons fail to differentiate from the onset in Runx3^-/- mice. By contrast, TrkC-positive DRG neurons differentiate normally at embryonic day (E) 11.5, but disappear by E13.5 in Runx3^-/- mice. Subsequently, TrkC-positive DRG neurons reappear but in smaller numbers than in the wild type. In Runx3^-/- mice, central axons of the TrkC-positive DRG neurons project to the dorsal spinal cord but not to the ventral and intermediate spinal cord, whereas the peripheral axons project to skin but not to muscle. These results suggest that Runx3 controls the acquisition of distinct proprioceptive DRG neuron identities, and that TrkC-positive DRG neurons consist of two subpopulations: Runx3-dependent early-appearing proprioceptive neurons that project to the ventral and intermediate spinal cord and muscle; and Runx3-independent late-appearing cutaneous neurons that project to the dorsal spinal cord and skin. Moreover, we show that the number of TrkA-positive DRG neurons is reduced in Runx3^-/- mice, as compared with the wild type. These results suggest that Runx3 positively regulates the expression of TrkC and TrkA in DRG neurons.