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 uncoordination 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.

AML1/Runx1 is important for the development of hindbrain cholinergic branchiovisceral motor neurons and selected cranial sensory neurons

“…An involvement of Runx1 in cranial sensory neuron differentiation is consistent with recent studies showing that Runx1 and the related gene Runx3 are expressed in separate dorsal root ganglion neuron subtypes. Runx1 is expressed in nociceptive neurons whereas Runx3 is found in proprioceptive neurons (12,15,24). Importantly, Runx3 inactivation causes a perturbation of the development of dorsal root ganglion proprioceptive, but not nociceptive, neurons (15,24).…”

“…Runx1 is expressed in nociceptive neurons whereas Runx3 is found in proprioceptive neurons (12,15,24). Importantly, Runx3 inactivation causes a perturbation of the development of dorsal root ganglion proprioceptive, but not nociceptive, neurons (15,24). Future studies aimed at further elucidating the involvement of Runx1 in cell survival and͞or differentiation events in selected sensory and motor neurons will provide important information that will help clarify mechanisms underlying the development of neuronal subtypes in the mammalian CNS and PNS.…”

Plasticity of DNA methylation in a nerve injury model of pain

“…25 Other Runx proteins have been reported to control the axonal projection of proprioceptive DRG neurons. 26 Hypermethylated alive deserts were enriched for SOX gene family (P < 10 ¡51 ) and neurofibromin 1 (NF1) binding sites (P < 10 ¡22 ). SOX genes are involved in neuronal development 27 and axon regeneration 28 and NF1 has long been recognized for its critical role in the PNS.…”

Exclusion of RUNX3 as a tumour-suppressor gene in early-onset gastric carcinomas

“…RUNX3, together with RUNX1 and RUNX2, makes up the RUNX family of genes, which play decisive roles in definitive haematopoiesis, osteogenesis, neurogenesis and thymopoiesis (Okuda et al, 1996;Komori et al, 1997;Inoue et al, 2002;Levanon et al, 2002;Taniuchi et al, 2002;Woolf et al, 2003). Their dysregulation has been linked to several pathologic conditions, including leukaemia and cleidocranial dysplasia (Lee et al, 1997;Mundlos et al, 1997).…”